Peters, S.
Pujol, J.-.
Dafni, U.
Dómine, M.
Popat, S.
Reck, M.
Andrade, J.
Becker, A.
Moro-Sibilot, D.
Curioni-Fontecedro, A.
Molinier, O.
Nackaerts, K.
Insa Mollá, A.
Gervais, R.
López Vivanco, G.
Madelaine, J.
Mazieres, J.
Faehling, M.
Griesinger, F.
Majem, M.
González Larriba, J.L.
Provencio Pulla, M.
Vervita, K.
Roschitzki-Voser, H.
Ruepp, B.
Mitchell, P.
Stahel, R.A.
Le Pechoux, C.
De Ruysscher, D.
Stahel, R.
Hiltbrunner, A.
Pardo-Contreras, M.
Gasca-Ruchti, A.
Giacomelli, N.
Kammler, R.
Marti, N.
Pfister, R.
Piguet, A.C.
Roux, S.
Troesch, S.
Schneider, M.
Schweri, R.
Zigomo, I.
Tsourti, Z.
Zygoura, P.
Tsouprou, S.
Kassapian, M.
Vervita, K.
Dimopoulou, G.
Andriakopoulou, C.
Morin, F.
Amour, E.
Mariaule, G.
Archirel, N.
Fernandez, M.
Pereira, E.
Benito, L.
Lopez, K.
Hernández, A.
Chinchen, S.
Jurkovic, H.
Livingstone, A.
Mitchell, J.
Walker, M.
Mitchell, P.
Ng, S.
Steer, C.
Briscoe, K.
Saqib, A.
Abdi, E.
Houghton, B.
O’Byrne, K.
Chittajallu, B.R.
Hughes, B.G.
Black, A.
Nackaerts, K.
Werner, H.
Gervais, R.
Zalcman, G.
Vaylet, F.
Merle, P.
Monnet, I.
Moro-Sibilot, D.
Molinier, O.
Girard, N.
Souquet, P.-.
Barlesi, F.
Debieuvre, D.
Senellart, H.
Poudenx, M.
Dixmier, A.
Pouessel, D.
Cadranel, J.
Lena, H.
Quoix, E.
Friard, S.
Audigier-Valette, C.
Mazieres, J.
Pichon, E.
Faehling, M.
Kokowski, K.
Kirchen, H.
Griesinger, F.
Tufman, A.
De-Colle, C.
de Langen, J.
González Larriba, J.L.
Insa, A.
Majem, M.
Massutí, B.
Pulla, M.P.
Aix, S.P.
Villanueva, N.
Vivanco, G.L.
Andrade, J.
Curioni-Fontecedro, A.
Franks, K.
Califano, R.
(2022). Consolidation nivolumab and ipilimumab versus observation in limited-disease small-cell lung cancer after chemo-radiotherapy – results from the randomised phase II ETOP/IFCT 4-12 STIMULI trial. Annals of oncology,
Vol.33
(1),
pp. 67-79.
Popat, S.
Baas, P.
Faivre-Finn, C.
Girard, N.
Nicholson, A.G.
Nowak, A.K.
Opitz, I.
Scherpereel, A.
Reck, M.
(2022). Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up☆. Annals of oncology,
Vol.33
(2),
pp. 129-142.
Coleman, N.
Harbery, A.
Heuss, S.
Vivanco, I.
Popat, S.
(2022). Targeting un-MET needs in advanced non-small cell lung cancer. Lung cancer,
Vol.164,
pp. 56-68.
Navani, N.
Baldwin, D.R.
Edwards, J.G.
Evison, M.
McDonald, F.
Nicholson, A.G.
Fenemore, J.
Sage, E.K.
Popat, S.
(2022). Lung Cancer in the United Kingdom. Journal of thoracic oncology,
Vol.17
(2),
pp. 186-193.
Peters, S.
Scherpereel, A.
Cornelissen, R.
Oulkhouir, Y.
Greillier, L.
Kaplan, M.A.
Talbot, T.
Monnet, I.
Hiret, S.
Baas, P.
Nowak, A.K.
Fujimoto, N.
Tsao, A.S.
Mansfield, A.S.
Popat, S.
Zhang, X.
Hu, N.
Balli, D.
Spires, T.
Zalcman, G.
(2022). First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743. Annals of oncology : official journal of the european society for medical oncology,
.
show abstract
Background
In the phase III CheckMate 743 study (NCT02899299), first-line nivolumab plus ipilimumab significantly improved overall survival (OS) versus chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM). We report updated data with 3-year minimum follow-up.
Patients and methods
Adults with previously untreated, histologically confirmed, unresectable MPM and Eastern Cooperative Oncology Group performance status of ≤1 were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks) for up to 2 years, or six cycles of platinum plus pemetrexed chemotherapy. This report includes updated efficacy and safety outcomes, exploratory biomarker analyses including four-gene inflammatory expression signature score, and a post hoc efficacy analysis in patients who discontinued treatment due to treatment-related adverse events (TRAEs).
Results
With a median follow-up of 43.1 months, nivolumab plus ipilimumab continued to prolong OS versus chemotherapy. Median OS was 18.1 versus 14.1 months [hazard ratio (95% confidence interval), 0.73 (0.61-0.87)], and 3-year OS rates were 23% versus 15%, respectively. Three-year progression-free survival rates were 14% versus 1%, and objective response rates were 40% versus 44%. At 3 years, 28% versus 0% of responders had an ongoing response. Improved survival benefit with nivolumab plus ipilimumab versus chemotherapy was observed across subgroups, including histology. A high score of the four-gene inflammatory signature appeared to correlate with improved survival benefit with nivolumab plus ipilimumab. No new safety signals were observed with nivolumab plus ipilimumab, despite patients being off therapy for 1 year. In patients who discontinued nivolumab plus ipilimumab due to TRAEs, median OS was 25.4 months, and 34% of responders maintained their responses for ≥3 years after discontinuation.
Conclusions
With 3 years' minimum follow-up, nivolumab plus ipilimumab continued to provide long-term survival benefit over chemotherapy and a manageable safety profile, supporting the regimen as standard-of-care treatment for unresectable MPM, regardless of histology..
Coker, E.A.
Stewart, A.
Ozer, B.
Minchom, A.R.
Pickard, L.
Ruddle, R.
Carreira, S.
Popat, S.
O'Brien, M.E.
Raynaud, F.I.
de Bono, J.S.
Al-Lazikani, B.
Banerji, U.
(2022). Individualised prediction of drug response and rational combination therapy in NSCLC using artificial intelligence enabled studies of acute phosphoproteomic changes. Molecular cancer therapeutics,
.
show abstract
We hypothesise the study of acute protein perturbation in signal transduction by targeted anticancer drugs can predict drug sensitivity of these agents used as single agents and rational combination therapy. We assayed dynamic changes in 52 phosphoproteins caused by acute exposure (1hr) to clinically-relevant concentrations of 7 targeted anticancer drugs in 35 non small-cell lung cancer (NSCLC) cell lines and 16 samples of NSCLC cells isolated from patient pleural effusions. We studied drug sensitivities across 35 cell lines and synergy of combinations of all drugs in six cell lines (252 combinations). We developed orthogonal machine-learning approaches to predict drug response and rational combination therapy. Our methods predicted the most and least sensitive quartiles of drug sensitivity with an AUC of 0.79 and 0.78 respectively, while predictions based on mutations in three genes commonly known to predict response to the drug studied e.g. EGFR, PIK3CA and KRAS, did not predict sensitivity (AUC 0.5 across all quartiles). The machine-learning predictions of combinations was compared to experimentally-generated data showed a bias to the highest quartile of Bliss synergy scores, p=0.0243. We confirmed feasibility of running such assays on 16 patient samples of freshly isolated NSCLC cells from pleural effusions. We have provided proof of concept for novel methods of using acute ex-vivo exposure of cancer cells to targeted anticancer drugs to predict response as single agents or combinations. These approaches could compliment current approaches using gene mutations/amplifications/rearrangements as biomarkers, and demonstrate the utility of proteomics data to inform treatment selection in the clinic..
Fendler, A.
Shepherd, S.T.
Au, L.
Wilkinson, K.A.
Wu, M.
Schmitt, A.M.
Tippu, Z.
Farag, S.
Rogiers, A.
Harvey, R.
Carlyle, E.
Edmonds, K.
Del Rosario, L.
Lingard, K.
Mangwende, M.
Holt, L.
Ahmod, H.
Korteweg, J.
Foley, T.
Barber, T.
Emslie-Henry, A.
Caulfield-Lynch, N.
Byrne, F.
Shum, B.
Gerard, C.L.
Deng, D.
Kjaer, S.
Song, O.-.
Queval, C.
Kavanagh, C.
Wall, E.C.
Carr, E.J.
Namjou, S.
Caidan, S.
Gavrielides, M.
MacRae, J.I.
Kelly, G.
Peat, K.
Kelly, D.
Murra, A.
Kelly, K.
O’Flaherty, M.
Shea, R.L.
Gardner, G.
Murray, D.
Popat, S.
Yousaf, N.
Jhanji, S.
Van As, N.
Young, K.
Furness, A.J.
Pickering, L.
Beale, R.
Swanton, C.
Gandhi, S.
Gamblin, S.
Bauer, D.L.
Kassiotis, G.
Howell, M.
Nicholson, E.
Walker, S.
Wilkinson, R.J.
Larkin, J.
Turajlic, S.
(2022). Immune responses following third COVID-19 vaccination are reduced in patients with hematological malignancies compared to patients with solid cancer. Cancer cell,
Vol.40
(4),
pp. 438-438.
O'Sullivan, H.
d'Arienzo, P.D.
Yousaf, N.
Cui, W.
Popat, S.
(2022). Inadequacy of PCR genotyping in advanced non-small cell lung cancer: EGFR L747_A755delinsSS exon 19 deletion is not detected by the real-time PCR Idylla™ EGFR mutation test but is detected by ctDNA next generation sequencing and responds to osimertinib. European journal of cancer,
Vol.166,
pp. 38-40.
Passaro, A.
Leighl, N.
Blackhall, F.
Popat, S.
Kerr, K.
Ahn, M.J.
Arcila, M.E.
Arrieta, O.
Planchard, D.
de Marinis, F.
Dingemans, A.M.
Dziadziuszko, R.
Faivre-Finn, C.
Feldman, J.
Felip, E.
Curigliano, G.
Herbst, R.
Jänne, P.A.
John, T.
Mitsudomi, T.
Mok, T.
Normanno, N.
Paz-Ares, L.
Ramalingam, S.
Sequist, L.
Vansteenkiste, J.
Wistuba, I.I.
Wolf, J.
Wu, Y.L.
Yang, S.R.
Yang, J.C.
Yatabe, Y.
Pentheroudakis, G.
Peters, S.
(2022). ESMO expert consensus statements on the management of EGFR mutant non-small-cell lung cancer. Annals of oncology,
Vol.33
(5),
pp. 466-487.
Scherpereel, A.
Antonia, S.
Bautista, Y.
Grossi, F.
Kowalski, D.
Zalcman, G.
Nowak, A.K.
Fujimoto, N.
Peters, S.
Tsao, A.S.
Mansfield, A.S.
Popat, S.
Sun, X.
Lawrance, R.
Zhang, X.
Daumont, M.J.
Bennett, B.
McKenna, M.
Baas, P.
(2022). First-line nivolumab plus ipilimumab versus chemotherapy for the treatment of unresectable malignant pleural mesothelioma: patient-reported outcomes in CheckMate 743. Lung cancer,
Vol.167,
pp. 8-16.
Reckamp, K.L.
Lin, H.M.
Cranmer, H.
Wu, Y.
Zhang, P.
Walton, L.J.
Kay, S.
Cichewicz, A.
Neupane, B.
Fahrbach, K.
Popat, S.
Camidge, D.R.
(2022). Indirect comparisons of brigatinib and alectinib for front-line ALK-positive non-small-cell lung cancer. Future oncology,
Vol.18
(20),
pp. 2499-2510.
show abstract
Aim: To conduct an indirect treatment comparison (ITC) of the relative efficacy of brigatinib and alectinib for progression-free survival in people with tyrosine kinase inhibitor (TKI)-naive ALK-positive non-small-cell lung cancer (NSCLC). Methods: Final aggregate and patient-level data from the ALTA-1L trial comparing brigatinib to crizotinib and published aggregate data from ALEX (comparing alectinib to crizotinib) were contrasted using Bucher ITC and matching-adjusted indirect comparisons (MAICs). Results: No statistically significant differences were identified between brigatinib and alectinib in reducing the risk of disease progression overall and in patients with baseline central nervous system metastases. Conclusion: Brigatinib appeared similar to alectinib in reducing risk of disease progression for people with TKI-naive ALK-positive NSCLC. .
Zauderer, M.G.
Szlosarek, P.W.
Le Moulec, S.
Popat, S.
Taylor, P.
Planchard, D.
Scherpereel, A.
Koczywas, M.
Forster, M.
Cameron, R.B.
Peikert, T.
Argon, E.K.
Michaud, N.R.
Szanto, A.
Yang, J.
Chen, Y.
Kansra, V.
Agarwal, S.
Fennell, D.A.
(2022). EZH2 inhibitor tazemetostat in patients with relapsed or refractory, BAP1-inactivated malignant pleural mesothelioma: a multicentre, open-label, phase 2 study. The lancet oncology,
Vol.23
(6),
pp. 758-767.
Luigi Banna, G.
Addeo, A.
Zygoura, P.
Tsourti, Z.
Popat, S.
Curioni-Fontecedro, A.
Nadal, E.
Shah, R.
Pope, A.
Fisher, P.
Spicer, J.
Roy, A.
Gilligan, D.
Gautschi, O.
Janthur, W.-.
López-Castro, R.
Roschitzki-Voser, H.
Dafni, U.
Peters, S.
Stahel, R.A.
(2022). A prognostic score for patients with malignant pleural mesothelioma (MPM) receiving second-line immunotherapy or chemotherapy in the ETOP 9–15 PROMISE-meso phase III trial. Lung cancer,
Vol.169,
pp. 77-83.
Cui, W.
Milner-Watts, C.
O'Sullivan, H.
Lyons, H.
Minchom, A.
Bhosle, J.
Davidson, M.
Yousaf, N.
Scott, S.
Faull, I.
Kushnir, M.
Nagy, R.
O'Brien, M.
Popat, S.
(2022). Up-front cell-free DNA next generation sequencing improves target identification in UK first line advanced non-small cell lung cancer (NSCLC) patients. European journal of cancer,
Vol.171,
pp. 44-54.
Popat, S.
Liu, S.V.
Scheuer, N.
Hsu, G.G.
Lockhart, A.
Ramagopalan, S.V.
Griesinger, F.
Subbiah, V.
(2022). Addressing challenges with real-world synthetic control arms to demonstrate the comparative effectiveness of Pralsetinib in non-small cell lung cancer. Nature communications,
Vol.13
(1).
show abstract
AbstractAs advanced non-small cell lung cancer (aNSCLC) is being increasingly divided into rare oncogene-driven subsets, conducting randomised trials becomes challenging. Using real-world data (RWD) to construct control arms for single-arm trials provides an option for comparative data. However, non-randomised treatment comparisons have the potential to be biased and cause concern for decision-makers. Using the example of pralsetinib from a RET fusion-positive aNSCLC single-arm trial (NCT03037385), we demonstrate a relative survival benefit when compared to pembrolizumab monotherapy and pembrolizumab with chemotherapy RWD cohorts. Quantitative bias analyses show that results for the RWD-trial comparisons are robust to data missingness, potential poorer outcomes in RWD and residual confounding. Overall, the study provides evidence in favour of pralsetinib as a first-line treatment for RET fusion-positive aNSCLC. The quantification of potential bias performed in this study can be used as a template for future studies of this nature..
Cui, W.
Milner-Watts, C.
McVeigh, T.P.
Minchom, A.
Bholse, J.
Davidson, M.
Yousaf, N.
MacMahon, S.
Mugalaasi, H.
Gunapala, R.
Lee, R.
George, A.
Popat, S.
O'Brien, M.
(2022). A pilot of Blood-First diagnostic cell free DNA (cfDNA) next generation sequencing (NGS) in patients with suspected advanced lung cancer. Lung cancer (amsterdam, netherlands),
Vol.165,
pp. 34-42.
show abstract
Introduction
The diagnostic pathway for lung cancer can be long. Availability of front-line targeted therapies for NSCLC demands access to good quality tissue for genomic sequencing and rapid reporting of results. Diagnosis of lung cancer and availability of tissue was delayed during the COVID-19 pandemic.
Methods
A pilot study assessing Guardant360™ cfDNA-NGS in patients with radiological-suspected advanced-stage lung cancer was performed at an academic cancer centre during COVID-19. Variants were tiered using AMP/ASCO/CAP guidelines and discussed at a tumour molecular board. The primary endpoint was the proportion of patients who commenced targeted treatment based on cfDNA-NGS results without tissue molecular results, predicted to be ≥ 10%.
Results
Between April 2020-May 2021, 51 patients were enrolled; 49 were evaluable. The median age was 71 years, 43% were never-smokers, 86% had stage IV disease. 80% of evaluable cfDNA-NGS were informative (tumour-derived cfDNA detected). cfDNA-NGS detected 30 (61%) AMP/ASCO/CAP tier 1 variants, including 20 additional tier 1 variants compared to tissue testing. Three patients with non-informative cfDNA-NGS had tier 1 variants identified on tissue testing. Eleven (22%; 95%CI 12%-27%) patients commenced targeted therapy based on cfDNA-NGS results without tissue molecular results, meeting the primary endpoint. Median time to results was shorter for cfDNA-NGS compared to standard-of-care tissue tests (9 versus 25 days, P < 0.0001).
Conclusion
Blood-first cfDNA-NGS in NSCLC patients increased the breadth and rapidity of detection of actionable variants with high tissue concordance and led to timely treatment decisions. A blood-first approach should be considered to improve the speed and accuracy of therapeutic decision-making..
Whisenant, J.G.
Baena, J.
Cortellini, A.
Huang, L.-.
Lo Russo, G.
Porcu, L.
Wong, S.K.
Bestvina, C.M.
Hellmann, M.D.
Roca, E.
Rizvi, H.
Monnet, I.
Boudjemaa, A.
Rogado, J.
Pasello, G.
Leighl, N.B.
Arrieta, O.
Aujayeb, A.
Batra, U.
Azzam, A.Y.
Unk, M.
Azab, M.A.
Zhumagaliyeva, A.N.
Gomez-Martin, C.
Blaquier, J.B.
Geraedts, E.
Mountzios, G.
Serrano-Montero, G.
Reinmuth, N.
Coate, L.
Marmarelis, M.
Presley, C.J.
Hirsch, F.R.
Garrido, P.
Khan, H.
Baggi, A.
Mascaux, C.
Halmos, B.
Ceresoli, G.L.
Fidler, M.J.
Scotti, V.
Métivier, A.-.
Falchero, L.
Felip, E.
Genova, C.
Mazieres, J.
Tapan, U.
Brahmer, J.
Bria, E.
Puri, S.
Popat, S.
Reckamp, K.L.
Morgillo, F.
Nadal, E.
Mazzoni, F.
Agustoni, F.
Bar, J.
Grosso, F.
Avrillon, V.
Patel, J.D.
Gomes, F.
Ibrahim, E.
Trama, A.
Bettini, A.C.
Barlesi, F.
Dingemans, A.-.
Wakelee, H.
Peters, S.
Horn, L.
Garassino, M.C.
Torri, V.
TERAVOLT study group,
(2022). A definitive prognostication system for patients with thoracic malignancies diagnosed with COVID-19: an update from the TERAVOLT registry. Journal of thoracic oncology : official publication of the international association for the study of lung cancer,
.
show abstract
Background
Patients with thoracic malignancies are at increased risk for mortality from Coronavirus disease 2019 (COVID-19) and large number of intertwined prognostic variables have been identified so far.
Methods
Capitalizing data from the TERAVOLT registry, a global study created with the aim of describing the impact of COVID-19 in patients with thoracic malignancies, we used a clustering approach, a fast-backward step-down selection procedure and a tree-based model to screen and optimize a broad panel of demographics, clinical COVID-19 and cancer characteristics.
Results
As of April 15, 2021, 1491 consecutive evaluable patients from 18 countries were included in the analysis. With a mean observation period of 42 days, 361 events were reported with an all-cause case fatality rate of 24.2%. The clustering procedure screened approximately 73 covariates in 13 clusters. A further multivariable logistic regression for the association between clusters and death was performed, resulting in five clusters significantly associated with the outcome. The fast-backward step-down selection then identified seven major determinants of death ECOG-PS (OR 2.47 1.87-3.26), neutrophil count (OR 2.46 1.76-3.44), serum procalcitonin (OR 2.37 1.64-3.43), development of pneumonia (OR 1.95 1.48-2.58), c-reactive protein (CRP) (OR 1.90 1.43-2.51), tumor stage at COVID-19 diagnosis (OR 1.97 1.46-2.66) and age (OR 1.71 1.29-2.26). The ROC analysis for death of the selected model confirmed its diagnostic ability (AUC 0.78; 95%CI: 0.75 - 0.81). The nomogram was able to classify the COVID-19 mortality in an interval ranging from 8% to 90% and the tree-based model recognized ECOG-PS, neutrophil count and CRP as the major determinants of prognosis.
Conclusion
From 73 variables analyzed, seven major determinants of death have been identified. Poor ECOG-PS demonstrated the strongest association with poor outcome from COVID-19. With our analysis we provide clinicians with a definitive prognostication system to help determine the risk of mortality for patients with thoracic malignancies and COVID-19..
Griesinger, F.
Cox, O.
Sammon, C.
Ramagopalan, S.V.
Popat, S.
(2022). Health technology assessments and real-world evidence: tell us what you want, what you really, really want. ,
Vol.11
(5),
pp. 297-299.
Popat, S.
Navani, N.
Kerr, K.M.
Smit, E.F.
Batchelor, T.J.
Van Schil, P.
Senan, S.
McDonald, F.
(2021). Navigating Diagnostic and Treatment Decisions in Non-Small Cell Lung Cancer: Expert Commentary on the Multidisciplinary Team Approach. The oncologist,
Vol.26
(2),
pp. e306-e315.
show abstract
Abstract
Non-small cell lung cancer (NSCLC) accounts for approximately one in five cancer-related deaths, and management requires increasingly complex decision making by health care professionals. Many centers have therefore adopted a multidisciplinary approach to patient care, using the expertise of various specialists to provide the best evidence-based, personalized treatment. However, increasingly complex disease staging, as well as expanded biomarker testing and multimodality management algorithms with novel therapeutics, have driven the need for multifaceted, collaborative decision making to optimally guide the overall treatment process. To keep up with the rapidly evolving treatment landscape, national-level guidelines have been introduced to standardize patient pathways and ensure prompt diagnosis and treatment. Such strategies depend on efficient and effective communication between relevant multidisciplinary team members and have both improved adherence to treatment guidelines and extended patient survival. This article highlights the value of a multidisciplinary approach to diagnosis and staging, treatment decision making, and adverse event management in NSCLC.
Implications for Practice
This review highlights the value of a multidisciplinary approach to the diagnosis and staging of non-small cell lung cancer (NSCLC) and makes practical suggestions as to how multidisciplinary teams (MDTs) can be best deployed at individual stages of the disease to improve patient outcomes and effectively manage common adverse events. The authors discuss how a collaborative approach, appropriately leveraging the diverse expertise of NSCLC MDT members (including specialist radiation and medical oncologists, chest physicians, pathologists, pulmonologists, surgeons, and nursing staff) can continue to ensure optimal per-patient decision making as treatment options become ever more specialized in the era of biomarker-driven therapeutic strategies.
.
Baas, P.
Scherpereel, A.
Nowak, A.K.
Fujimoto, N.
Peters, S.
Tsao, A.S.
Mansfield, A.S.
Popat, S.
Jahan, T.
Antonia, S.
Oulkhouir, Y.
Bautista, Y.
Cornelissen, R.
Greillier, L.
Grossi, F.
Kowalski, D.
Rodríguez-Cid, J.
Aanur, P.
Oukessou, A.
Baudelet, C.
Zalcman, G.
(2021). First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. The lancet,
Vol.397
(10272),
pp. 375-386.
Chang, W.
Zhang, Y.Z.
Wolf, J.L.
Hermelijn, S.M.
Schnater, J.M.
Thüsen, J.H.
Rice, A.
Lantuejoul, S.
Mastroianni, B.
Farver, C.
Black, F.
Popat, S.
Nicholson, A.G.
(2021). Mucinous adenocarcinoma arising in congenital pulmonary airway malformation: clinicopathological analysis of 37 cases. Histopathology,
Vol.78
(3),
pp. 434-444.
Yang, J.C.
Reckamp, K.L.
Kim, Y.-.
Novello, S.
Smit, E.F.
Lee, J.-.
Su, W.-.
Akerley, W.L.
Blakely, C.M.
Groen, H.J.
Bazhenova, L.
Carcereny Costa, E.
Chiari, R.
Hsia, T.-.
Golsorkhi, T.
Despain, D.
Shih, D.
Popat, S.
Wakelee, H.
(2021). Efficacy and Safety of Rociletinib Versus Chemotherapy in Patients With EGFR-Mutated NSCLC: The Results of TIGER-3, a Phase 3 Randomized Study. Jto clinical and research reports,
Vol.2
(2),
pp. 100114-100114.
Joshi, K.
Muhith, A.
Obeid, M.
Milner-Watts, C.
Yousaf, N.
Popat, S.
Davidson, M.
Bhosle, J.
O’Brien, M.
Minchom, A.
(2021). Safety monitoring of two and four-weekly adjuvant durvalumab for patients with stage III NSCLC: implications for the COVID-19 pandemic and beyond. Lung cancer,
Vol.156,
pp. 147-150.
Cui, W.
Popat, S.
(2021). Immune Checkpoint Inhibition for Unresectable Malignant Pleural Mesothelioma. Drugs,
Vol.81
(9),
pp. 971-984.
Adizie, J.B.
Tweedie, J.
Khakwani, A.
Peach, E.
Hubbard, R.
Wood, N.
Gosney, J.R.
Harden, S.V.
Beckett, P.
Popat, S.
Navani, N.
(2021). Biomarker Testing for People With Advanced Lung Cancer in England. Jto clinical and research reports,
Vol.2
(6),
pp. 100176-100176.
Manickavasagar, T.
Yuan, W.
Carreira, S.
Gurel, B.
Miranda, S.
Ferreira, A.
Crespo, M.
Riisnaes, R.
Baker, C.
O'Brien, M.
Bhosle, J.
Popat, S.
Banerji, U.
Lopez, J.
de Bono, J.
Minchom, A.
(2021). HER3 expression and MEK activation in non-small-cell lung carcinoma. Lung cancer management,
,
pp. ?-? (12).
Nicholson, A.G.
Moreira, A.L.
Mino-Kenudson, M.
Popat, S.
(2021). Grading in Lung Adenocarcinoma: Another New Normal. Journal of thoracic oncology,
Vol.16
(10),
pp. 1601-1604.
Popat, S.
Sharma, B.
MacMahon, S.
Nicholson, A.G.
Sharma, R.K.
Schuster, K.
Lang Lazdunski, L.
Fennell, D.
(2021). Durable Response to Vismodegib in PTCH1 F1147fs Mutant Relapsed Malignant Pleural Mesothelioma: Implications for Mesothelioma Drug Treatment. Jco precision oncology,
(5),
pp. 39-43.
Cui, W.
Popat, S.
(2021). Pleural mesothelioma (PM) – The status of systemic therapy. Cancer treatment reviews,
Vol.100,
pp. 102265-102265.
Nastase, A.
Mandal, A.
Lu, S.K.
Anbunathan, H.
Morris-Rosendahl, D.
Zhang, Y.Z.
Sun, X.-.
Gennatas, S.
Rintoul, R.C.
Edwards, M.
Bowman, A.
Chernova, T.
Benepal, T.
Lim, E.
Taylor, A.N.
Nicholson, A.G.
Popat, S.
Willis, A.E.
MacFarlane, M.
Lathrop, M.
Bowcock, A.M.
Moffatt, M.F.
Cookson, W.O.
(2021). Integrated genomics point to immune vulnerabilities in pleural mesothelioma. Scientific reports,
Vol.11
(1).
show abstract
AbstractPleural mesothelioma is an aggressive malignancy with limited effective therapies. In order to identify therapeutic targets, we integrated SNP genotyping, sequencing and transcriptomics from tumours and low-passage patient-derived cells. Previously unrecognised deletions of SUFU locus (10q24.32), observed in 21% of 118 tumours, resulted in disordered expression of transcripts from Hedgehog pathways and the T-cell synapse including VISTA. Co-deletion of Interferon Type I genes and CDKN2A was present in half of tumours and was a predictor of poor survival. We also found previously unrecognised deletions in RB1 in 26% of cases and show sub-micromolar responses to downstream PLK1, CHEK1 and Aurora Kinase inhibitors in primary mesothelioma cells. Defects in Hippo pathways that included RASSF7 amplification and NF2 or LATS1/2 mutations were present in 50% of tumours and were accompanied by micromolar responses to the YAP1 inhibitor Verteporfin. Our results suggest new therapeutic avenues in mesothelioma and indicate targets and biomarkers for immunotherapy..
Willis-Owen, S.A.
Domingo-Sabugo, C.
Starren, E.
Liang, L.
Freidin, M.B.
Arseneault, M.
Zhang, Y.
Lu, S.K.
Popat, S.
Lim, E.
Nicholson, A.G.
Riazalhosseini, Y.
Lathrop, M.
Cookson, W.O.
Moffatt, M.F.
(2021). Y disruption, autosomal hypomethylation and poor male lung cancer survival. Scientific reports,
Vol.11
(1),
pp. 12453-?.
show abstract
Lung cancer is the most frequent cause of cancer death worldwide. It affects more men than women, and men generally have worse survival outcomes. We compared gene co-expression networks in affected and unaffected lung tissue from 126 consecutive patients with Stage IA-IV lung cancer undergoing surgery with curative intent. We observed marked degradation of a sex-associated transcription network in tumour tissue. This disturbance, detected in 27.7% of male tumours in the discovery dataset and 27.3% of male tumours in a further 123-sample replication dataset, was coincident with partial losses of the Y chromosome and extensive autosomal DNA hypomethylation. Central to this network was the epigenetic modifier and regulator of sexually dimorphic gene expression, KDM5D. After accounting for prognostic and epidemiological covariates including stage and histology, male patients with tumour KDM5D deficiency showed a significantly increased risk of death (Hazard Ratio [HR] 3.80, 95% CI 1.40-10.3, P = 0.009). KDM5D deficiency was confirmed as a negative prognostic indicator in a further 1100 male lung tumours (HR 1.67, 95% CI 1.4-2.0, P = 1.2 × 10 -10 ). Our findings identify tumour deficiency of KDM5D as a prognostic marker and credible mechanism underlying sex disparity in lung cancer..
Camidge, D.R.
Kim, H.R.
Ahn, M.-.
Yang, J.C.
Han, J.-.
Hochmair, M.J.
Lee, K.H.
Delmonte, A.
Garcia Campelo, M.R.
Kim, D.-.
Griesinger, F.
Felip, E.
Califano, R.
Spira, A.I.
Gettinger, S.N.
Tiseo, M.
Lin, H.M.
Liu, Y.
Vranceanu, F.
Niu, H.
Zhang, P.
Popat, S.
(2021). Brigatinib Versus Crizotinib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial. Journal of thoracic oncology : official publication of the international association for the study of lung cancer,
.
show abstract
Introduction In the phase 3 study entitled ALK in Lung cancer Trial of brigAtinib in 1st Line (ALTA-1L), which is a study of brigatinib in ALK inhibitor-naive advanced ALK-positive NSCLC, brigatinib exhibited superior progression-free survival (PFS) versus crizotinib in the two planned interim analyses. Here, we report the final efficacy, safety, and exploratory results. Methods Patients were randomized to brigatinib 180 mg once daily (7-d lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. The primary end point was a blinded independent review committee-assessed PFS. Genetic alterations in plasma cell-free DNA were assessed in relation to clinical efficacy. Results A total of 275 patients were enrolled (brigatinib, n = 137; crizotinib, n = 138). At study end, (brigatinib median follow-up = 40.4 mo), the 3-year PFS by blinded independent review committee was 43% (brigatinib) versus 19% (crizotinib; median = 24.0 versus 11.1 mo, hazard ratio [HR] = 0.48, 95% confidence interval [CI]: 0.35-0.66). The median overall survival was not reached in either group (HR = 0.81, 95% CI: 0.53-1.22). Posthoc analyses suggested an overall survival benefit for brigatinib in patients with baseline brain metastases (HR = 0.43, 95% CI: 0.21-0.89). Detectable baseline EML4-ALK fusion variant 3 and TP53 mutation in plasma were associated with poor PFS. Brigatinib exhibited superior efficacy compared with crizotinib regardless of EML4-ALK variant and TP53 mutation. Emerging secondary ALK mutations were rare in patients progressing on brigatinib. No new safety signals were observed. Conclusions In the ALTA-1L final analysis, with longer follow-up, brigatinib continued to exhibit superior efficacy and tolerability versus crizotinib in patients with or without poor prognostic biomarkers. The suggested survival benefit with brigatinib in patients with brain metastases warrants future study..
Popat, S.
Jung, H.A.
Lee, S.Y.
Hochmair, M.J.
Lee, S.H.
Escriu, C.
Lee, M.K.
Migliorino, M.R.
Lee, Y.C.
Girard, N.
Daoud, H.
Märten, A.
Miura, S.
(2021). Sequential afatinib and osimertinib in patients with EGFR mutation-positive NSCLC and acquired T790M: A global non-interventional study (UpSwinG). Lung cancer (amsterdam, netherlands),
Vol.162,
pp. 9-15.
show abstract
Background Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard of care for EGFR mutation-positive non-small cell lung cancer (NSCLC). However, optimal sequence of treatment has yet to be defined. Overall survival (OS) is influenced by the availability/use of subsequent therapy after first-line treatment. Emergence of T790M is the main mechanism of resistance to afatinib and second-line osimertinib could be a treatment option in this instance. Methods In this non-interventional, global study (NCT04179890), existing medical/electronic records were identified for consecutive EGFR TKI-naïve patients with EGFR mutation-positive NSCLC (Del19 or L858R) treated with first-line afatinib and second-line osimertinib in regular clinical practice (n = 191; all T790M-positive). The primary objective was time to treatment failure (TTF). Key secondary objectives were OS and objective response rate (ORR). Results At the start of afatinib treatment, median age (range) was 62 years (34-88). Fifty-five percent of patients were female and 67% were Asian. ECOG PS (0/1/≥2) was 31%/57%/12%. Fourteen percent of patients had brain metastases. At the start of osimertinib treatment, ECOG PS (0/1/≥2) was 25%/61%/14% and 14% had brain metastases (rising to 29% at the end of osimertinib treatment). The source of biopsy material (solid/liquid) was 86%/3% at the start of afatinib and 54%/33% at start of osimertinib. Mutations were mainly detected with PCR methods. Overall, median TTF was 27.7 months (95% CI: 24.0-30.2) and median OS was 36.5 months (95% CI: 32.9-41.8). ORR with afatinib and osimertinib was 74% and 45%. TTF, OS and ORR were generally consistent across subgroups. Conclusion Sequential afatinib and osimertinib demonstrated encouraging activity in patients with EGFR mutation-positive NSCLC and acquired T790M. Activity was observed across all subgroups, including patients with poor ECOG PS or brain metastases. ECOG PS and incidence of brain metastases remained stable prior to, and after, afatinib treatment..
Lindsay, C.R.
Shaw, E.C.
Moore, D.A.
Rassl, D.
Jamal-Hanjani, M.
Steele, N.
Naheed, S.
Dick, C.
Taylor, F.
Adderley, H.
Black, F.
Summers, Y.
Evans, M.
Rice, A.
Fabre, A.
Wallace, W.A.
Nicholson, S.
Haragan, A.
Taniere, P.
Nicholson, A.G.
Laing, G.
Cave, J.
Forster, M.D.
Blackhall, F.
Gosney, J.
Popat, S.
Kerr, K.M.
(2021). Large cell neuroendocrine lung carcinoma: consensus statement from The British Thoracic Oncology Group and the Association of Pulmonary Pathologists. British journal of cancer,
Vol.125
(9),
pp. 1210-1216.
show abstract
AbstractOver the past 10 years, lung cancer clinical and translational research has been characterised by exponential progress, exemplified by the introduction of molecularly targeted therapies, immunotherapy and chemo-immunotherapy combinations to stage III and IV non-small cell lung cancer. Along with squamous and small cell lung cancers, large cell neuroendocrine carcinoma (LCNEC) now represents an area of unmet need, particularly hampered by the lack of an encompassing pathological definition that can facilitate real-world and clinical trial progress. The steps we have proposed in this article represent an iterative and rational path forward towards clinical breakthroughs that can be modelled on success in other lung cancer pathologies..
Ou, S.-.
Gadgeel, S.M.
Barlesi, F.
Yang, J.C.
De Petris, L.
Kim, D.-.
Govindan, R.
Dingemans, A.-.
Crino, L.
Léna, H.
Popat, S.
Ahn, J.S.
Dansin, E.
Mitry, E.
Müller, B.
Bordogna, W.
Balas, B.
Morcos, P.N.
Shaw, A.T.
(2020). Pooled overall survival and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small-cell lung cancer. Lung cancer,
Vol.139,
pp. 22-27.
Camidge, D.R.
Kim, H.R.
Ahn, M.-.
Yang, J.C.
Han, J.-.
Hochmair, M.J.
Lee, K.H.
Delmonte, A.
García Campelo, M.R.
Kim, D.-.
Griesinger, F.
Felip, E.
Califano, R.
Spira, A.
Gettinger, S.N.
Tiseo, M.
Lin, H.M.
Gupta, N.
Hanley, M.J.
Ni, Q.
Zhang, P.
Popat, S.
(2020). Brigatinib Versus Crizotinib in Advanced ALK Inhibitor–Naive ALK-Positive Non–Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial. Journal of clinical oncology,
Vol.38
(31),
pp. 3592-3603.
show abstract
PURPOSE Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, demonstrated superior progression-free survival (PFS) and improved health-related quality of life (QoL) versus crizotinib in advanced ALK inhibitor–naive ALK-positive non–small cell lung cancer (NSCLC) at first interim analysis (99 events; median brigatinib follow-up, 11.0 months) in the open-label, phase III ALTA-1L trial (ClinicalTrials.gov identifier: NCT02737501 ). We report results of the second prespecified interim analysis (150 events). METHODS Patients with ALK inhibitor–naive advanced ALK-positive NSCLC were randomly assigned 1:1 to brigatinib 180 mg once daily (7-day lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. The primary end point was PFS as assessed by blinded independent review committee (BIRC). Investigator-assessed efficacy, blood samples for pharmacokinetic assessments, and patient-reported outcomes were also collected. RESULTS Two hundred seventy-five patients were randomly assigned (brigatinib, n = 137; crizotinib, n = 138). With median follow-up of 24.9 months for brigatinib (150 PFS events), brigatinib showed consistent superiority in BIRC-assessed PFS versus crizotinib (hazard ratio [HR], 0.49 [95% CI, 0.35 to 0.68]; log-rank P < .0001; median, 24.0 v 11.0 months). Investigator-assessed PFS HR was 0.43 (95% CI, 0.31 to 0.61; median, 29.4 v 9.2 months). No new safety concerns emerged. Brigatinib delayed median time to worsening of global health status/QoL scores compared with crizotinib (HR, 0.70 [95% CI, 0.49 to 1.00]; log-rank P = .049). Brigatinib daily area under the plasma concentration–time curve was not a predictor of PFS (HR, 1.005 [95% CI, 0.98 to 1.031]; P = .69). CONCLUSION Brigatinib represents a once-daily ALK inhibitor with superior efficacy, tolerability, and QoL over crizotinib, making it a promising first-line treatment of ALK-positive NSCLC. .
Felip, E.
Ardizzoni, A.
Ciuleanu, T.
Cobo, M.
Laktionov, K.
Szilasi, M.
Califano, R.
Carcereny, E.
Griffiths, R.
Paz-Ares, L.
Duchnowska, R.
Garcia, M.A.
Isla, D.
Jassem, J.
Appel, W.
Milanowski, J.
Van Meerbeeck, J.P.
Wolf, J.
Li, A.
Acevedo, A.
Popat, S.
(2020). CheckMate 171: A phase 2 trial of nivolumab in patients with previously treated advanced squamous non-small cell lung cancer, including ECOG PS 2 and elderly populations. European journal of cancer,
Vol.127,
pp. 160-172.
Zhang, Y.Z.
Brambilla, C.
Molyneaux, P.L.
Rice, A.
Robertus, J.L.
Jordan, S.
Lim, E.
Lang-Lazdunski, L.
Begum, S.
Dusmet, M.
Anikin, V.
Beddow, E.
Finch, J.
Asadi, N.
Popat, S.
Cookson, W.O.
Moffatt, M.F.
Nicholson, A.G.
(2020). Utility of Nuclear Grading System in Epithelioid Malignant Pleural Mesothelioma in Biopsy-heavy Setting. American journal of surgical pathology,
Vol.44
(3),
pp. 347-356.
Minchom, A.
Yuan, W.
Crespo, M.
Gurel, B.
Figueiredo, I.
Wotherspoon, A.
Miranda, S.
Riisnaes, R.
Ferreira, A.
Bertan, C.
Pereira, R.
Clarke, M.
Baker, C.
Ang, J.E.
Fotiadis, N.
Tunariu, N.
Carreira, S.
Popat, S.
O'Brien, M.
Banerji, U.
de Bono, J.
Lopez, J.
(2020). Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab. Journal for immunotherapy of cancer,
Vol.8
(1).
show abstract
Background This case represents an exceptional response to pembrolizumab in a patient with epithelioid mesothelioma with a further response on rechallenge.Case presentation A 77-year-old woman with advanced epithelioid mesothelioma extensively pretreated with chemotherapy demonstrated a prolonged response of 45 months to 52 cycles of pembrolizumab. On rechallenge with pembrolizumab, further disease stability was achieved. Serial biopsies and analysis by immunohistochemistry and immunofluorescence demonstrated marked immune infiltration and documented the emergency of markers of immune exhaustion. Whole exome sequencing demonstrated a reduction in tumor mutational burden consistent with subclone elimination by immune checkpoint inhibitor (CPI) therapy. The relapse biopsy had missense mutation in BTN2A1.Conclusion This case supports rechallenge of programme death receptor 1 inhibitor in cases of previous CPI sensitivity and gives molecular insights..
Yang, J.C.
Schuler, M.
Popat, S.
Miura, S.
Heeke, S.
Park, K.
Märten, A.
Kim, E.S.
(2020). Afatinib for the Treatment of NSCLC Harboring Uncommon EGFR Mutations: A Database of 693 Cases. Journal of thoracic oncology,
Vol.15
(5),
pp. 803-815.
Remon, J.
Passiglia, F.
Ahn, M.-.
Barlesi, F.
Forde, P.M.
Garon, E.B.
Gettinger, S.
Goldberg, S.B.
Herbst, R.S.
Horn, L.
Kubota, K.
Lu, S.
Mezquita, L.
Paz-Ares, L.
Popat, S.
Schalper, K.A.
Skoulidis, F.
Reck, M.
Adjei, A.A.
Scagliotti, G.V.
(2020). Immune Checkpoint Inhibitors in Thoracic Malignancies: Review of the Existing Evidence by an IASLC Expert Panel and Recommendations. Journal of thoracic oncology,
Vol.15
(6),
pp. 914-947.
Popat, S.
Grohé, C.
Corral, J.
Reck, M.
Novello, S.
Gottfried, M.
Radonjic, D.
Kaiser, R.
(2020). Anti-angiogenic agents in the age of resistance to immune checkpoint inhibitors: Do they have a role in non-oncogene-addicted non-small cell lung cancer?. Lung cancer,
Vol.144,
pp. 76-84.
Evison, M.
Edwards, J.
McDonald, F.
Popat, S.
(2020). Stage III Non-small Cell Lung Cancer: A UK National Survey of Practice. Clinical oncology,
Vol.32
(8),
pp. 527-536.
Coleman, N.
Yousaf, N.
Arkenau, H.-.
Welsh, L.
Popat, S.
(2020). Lorlatinib Salvages Central Nervous System–Only Relapse on Entrectinib in ROS1-Positive NSCLC. Journal of thoracic oncology,
Vol.15
(8),
pp. e142-e144.
Lim, E.
Darlison, L.
Edwards, J.
Elliott, D.
Fennell, D.A.
Popat, S.
Rintoul, R.C.
Waller, D.
Ali, C.
Bille, A.
Fuller, L.
Ionescu, A.
Keni, M.
Kirk, A.
Koh, P.
Lau, K.
Mansy, T.
Maskell, N.A.
Milton, R.
Muthukumar, D.
Pope, T.
Roy, A.
Shah, R.
Shamash, J.
Tasigiannopoulos, Z.
Taylor, P.
Treece, S.
Ashton, K.
Harris, R.
Joyce, K.
Warnes, B.
Mills, N.
Stokes, E.A.
Rogers, C.
(2020). Mesothelioma and Radical Surgery 2 (MARS 2): protocol for a multicentre randomised trial comparing (extended) pleurectomy decortication versus no (extended) pleurectomy decortication for patients with malignant pleural mesothelioma. Bmj open,
Vol.10
(9),
pp. e038892-e038892.
show abstract
IntroductionMesothelioma remains a lethal cancer. To date, systemic therapy with pemetrexed and a platinum drug remains the only licensed standard of care. As the median survival for patients with mesothelioma is 12.1 months, surgery is an important consideration to improve survival and/or quality of life. Currently, only two surgical trials have been performed which found that neither extensive (extra-pleural pneumonectomy) or limited (partial pleurectomy) surgery improved survival (although there was some evidence of improved quality of life). Therefore, clinicians are now looking to evaluate pleurectomy decortication, the only radical treatment option left.Methods and analysisThe MARS 2 study is a UK multicentre open parallel group randomised controlled trial comparing the effectiveness and cost-effectiveness of surgery—(extended) pleurectomy decortication—versus no surgery for the treatment of pleural mesothelioma. The study will test the hypothesis that surgery and chemotherapy is superior to chemotherapy alone with respect to overall survival. Secondary outcomes include health-related quality of life, progression-free survival, measures of safety (adverse events) and resource use to 2 years. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment.Ethics and disseminationResearch ethics approval was granted by London – Camberwell St. Giles Research Ethics Committee (reference 13/LO/1481) on 7 November 2013. We will submit the results for publication in a peer-reviewed journal.Trial registration numbersISRCTN—ISRCTN44351742 and ClinicalTrials.gov—NCT02040272..
Middleton, G.
Brock, K.
Savage, J.
Mant, R.
Summers, Y.
Connibear, J.
Shah, R.
Ottensmeier, C.
Shaw, P.
Lee, S.-.
Popat, S.
Barrie, C.
Barone, G.
Billingham, L.
(2020). Pembrolizumab in patients with non-small-cell lung cancer of performance status 2 (PePS2): a single arm, phase 2 trial. The lancet respiratory medicine,
Vol.8
(9),
pp. 895-904.
Zhang, Y.Z.
Brambilla, C.
Molyneaux, P.L.
Rice, A.
Robertus, J.L.
Jordan, S.
Lim, E.
Lang‐Lazdunski, L.
Begum, S.
Dusmet, M.
Anikin, V.
Beddow, E.
Finch, J.
Asadi, N.
Popat, S.
Quesne, J.L.
Husain, A.N.
Cookson, W.O.
Moffatt, M.F.
Nicholson, A.G.
(2020). Presence of pleomorphic features but not growth patterns improves prognostic stratification of epithelioid malignant pleural mesothelioma by 2‐tier nuclear grade. Histopathology,
Vol.77
(3),
pp. 423-436.
Bartlett, E.C.
Kemp, S.V.
Ridge, C.A.
Desai, S.R.
Mirsadraee, S.
Morjaria, J.B.
Shah, P.L.
Popat, S.
Nicholson, A.G.
Rice, A.J.
Jordan, S.
Begum, S.
Mani, A.
Derbyshire, J.
Morris, K.
Chen, M.
Peacock, C.
Addis, J.
Martins, M.
Kaye, S.B.
Padley, S.P.
Devaraj, A.
McDonald, F.
Robertus, J.L.
Lim, E.
Barnett, J.
Finch, J.
Dalal, P.
Yousaf, N.
Jamali, A.
Ivashniova, N.
Phillips, C.
Newsom-Davies, T.
Lee, R.
Vaghani, P.
Whiteside, S.
Vaughan-Smith, S.
(2020). Baseline Results of the West London lung cancer screening pilot study – Impact of mobile scanners and dual risk model utilisation. Lung cancer,
Vol.148,
pp. 12-19.
Tokaca, N.
Cui, W.
Hazell, S.
Nicholson, A.G.
Van As, N.
Popat, S.
(2020). Squamous Non–Small-Cell Lung Cancer Molecularly Reclassified as Transdifferentiated Prostate Cancer Due to Identification of TMPRSS2-ERG Translocation With SOX2 Amplification. Jco oncology practice,
Vol.16
(10),
pp. 695-697.
Coleman, N.
Woolf, D.
Welsh, L.
McDonald, F.
MacMahon, S.
Yousaf, N.
Popat, S.
(2020). EGFR Exon 20 Insertion (A763_Y764insFQEA) Mutant NSCLC Is Not Identified by Roche Cobas Version 2 Tissue Testing but Has Durable Intracranial and Extracranial Response to Osimertinib. Journal of thoracic oncology,
Vol.15
(10),
pp. e162-e165.
Popat, S.
Curioni-Fontecedro, A.
Dafni, U.
Shah, R.
O'Brien, M.
Pope, A.
Fisher, P.
Spicer, J.
Roy, A.
Gilligan, D.
Gautschi, O.
Nadal, E.
Janthur, W.D.
López Castro, R.
García Campelo, R.
Rusakiewicz, S.
Letovanec, I.
Polydoropoulou, V.
Roschitzki-Voser, H.
Ruepp, B.
Gasca-Ruchti, A.
Peters, S.
Stahel, R.A.
(2020). A multicentre randomised phase III trial comparing pembrolizumab versus single-agent chemotherapy for advanced pre-treated malignant pleural mesothelioma: the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial. Annals of oncology,
Vol.31
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pp. 1734-1745.
Cui, W.
Cotter, C.
Sreter, K.B.
Heelan, K.
Creamer, D.
Basu, T.N.
Handy, J.
Walsh, S.
Popat, S.
(2020). Case of Fatal Immune-Related Skin Toxicity From Sequential Use of Osimertinib After Pembrolizumab: Lessons for Drug Sequencing in Never-Smoking Non–Small-Cell Lung Cancer. Jco oncology practice,
Vol.16
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pp. 842-844.
Middleton, G.
Fletcher, P.
Popat, S.
Savage, J.
Summers, Y.
Greystoke, A.
Gilligan, D.
Cave, J.
O’Rourke, N.
Brewster, A.
Toy, E.
Spicer, J.
Jain, P.
Dangoor, A.
Mackean, M.
Forster, M.
Farley, A.
Wherton, D.
Mehmi, M.
Sharpe, R.
Mills, T.C.
Cerone, M.A.
Yap, T.A.
Watkins, T.B.
Lim, E.
Swanton, C.
Billingham, L.
(2020). Publisher Correction: The National Lung Matrix Trial of personalized therapy in lung cancer. Nature,
Vol.585
(7826),
pp. E21-E21.
Middleton, G.
Fletcher, P.
Popat, S.
Savage, J.
Summers, Y.
Greystoke, A.
Gilligan, D.
Cave, J.
O’Rourke, N.
Brewster, A.
Toy, E.
Spicer, J.
Jain, P.
Dangoor, A.
Mackean, M.
Forster, M.
Farley, A.
Wherton, D.
Mehmi, M.
Sharpe, R.
Mills, T.C.
Cerone, M.A.
Yap, T.A.
Watkins, T.B.
Lim, E.
Swanton, C.
Billingham, L.
(2020). The National Lung Matrix Trial of personalized therapy in lung cancer. Nature,
Vol.583
(7818),
pp. 807-812.
Lim, K.H.
Popat, S.
(2020). Highlights in lung cancer in 2019. Esmo open,
Vol.5
(1),
pp. e000676-e000676.
Reck, M.
Kerr, K.M.
Grohé, C.
Manegold, C.
Pavlakis, N.
Paz-Ares, L.
Huber, R.M.
Popat, S.
Thatcher, N.
Park, K.
Hilberg, F.
Barrueco, J.
Kaiser, R.
(2019). Defining aggressive or early progressing nononcogene-addicted non-small-cell lung cancer: a separate disease entity?. Future oncology (london, england),
Vol.15
(12),
pp. 1363-1383.
show abstract
A substantial proportion of patients with nononcogene-addicted non-small-cell lung cancer (NSCLC) has 'aggressive disease', as reflected in short time to progression or lack of disease control with initial platinum-based chemotherapy. Recently, clinical correlates of aggressive disease behavior during first-line therapy have been shown to predict greater benefit from addition of nintedanib to second-line docetaxel in adenocarcinoma NSCLC. Positive predictive effects of aggressive disease have since been reported with other anti-angiogenic agents (ramucirumab and bevacizumab), while such features may negatively impact on outcomes with nivolumab in nonsquamous NSCLC with low PD-L1 expression. Based on a review of the clinical data, we recommend aggressive nonsquamous NSCLC should be defined by progression within <6-9 months of first-line treatment initiation..
Tsao, A.
Nakano, T.
Nowak, A.K.
Popat, S.
Scagliotti, G.V.
Heymach, J.
(2019). Targeting angiogenesis for patients with unresectable malignant pleural mesothelioma. Seminars in oncology,
Vol.46
(2),
pp. 145-154.
Califano, R.
Hochmair, M.J.
Gridelli, C.
Delmonte, A.
Garcia Campelo, M.R.
Bearz, A.
Griesinger, F.
Morabito, A.
Felip, E.
Ghosh, S.
Tiseo, M.
Haney, J.
Kerstein, D.
Popat, S.
Camidge, D.R.
(2019). Brigatinib (BRG) vs crizotinib (CRZ) in the phase III ALTA-1L trial. Annals of oncology,
Vol.30,
pp. ii48-ii48.
Planchard, D.
Popat, S.
Kerr, K.
Novello, S.
Smit, E.F.
Faivre-Finn, C.
Mok, T.S.
Reck, M.
Van Schil, P.E.
Hellmann, M.D.
Peters, S.
(2019). Correction to: “Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up”. Annals of oncology,
Vol.30
(5),
pp. 863-870.
Scagliotti, G.V.
Gaafar, R.
Nowak, A.K.
Nakano, T.
van Meerbeeck, J.
Popat, S.
Vogelzang, N.J.
Grosso, F.
Aboelhassan, R.
Jakopovic, M.
Ceresoli, G.L.
Taylor, P.
Orlandi, F.
Fennell, D.A.
Novello, S.
Scherpereel, A.
Kuribayashi, K.
Cedres, S.
Sørensen, J.B.
Pavlakis, N.
Reck, M.
Velema, D.
von Wangenheim, U.
Kim, M.
Barrueco, J.
Tsao, A.S.
(2019). Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial. The lancet respiratory medicine,
Vol.7
(7),
pp. 569-580.
Mazieres, J.
Drilon, A.
Lusque, A.
Mhanna, L.
Cortot, A.B.
Mezquita, L.
Thai, A.A.
Mascaux, C.
Couraud, S.
Veillon, R.
Van den Heuvel, M.
Neal, J.
Peled, N.
Früh, M.
Ng, T.L.
Gounant, V.
Popat, S.
Diebold, J.
Sabari, J.
Zhu, V.W.
Rothschild, S.I.
Bironzo, P.
Martinez-Marti, A.
Curioni-Fontecedro, A.
Rosell, R.
Lattuca-Truc, M.
Wiesweg, M.
Besse, B.
Solomon, B.
Barlesi, F.
Schouten, R.D.
Wakelee, H.
Camidge, D.R.
Zalcman, G.
Novello, S.
Ou, S.I.
Milia, J.
Gautschi, O.
(2019). Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Annals of oncology : official journal of the european society for medical oncology,
Vol.30
(8),
pp. 1321-1328.
show abstract
Background Anti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction.Patients and methods We conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation.Results We studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2).Conclusions : ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent..
Coleman, N.
Wotherspoon, A.
Yousaf, N.
Popat, S.
(2019). Transformation to neuroendocrine carcinoma as a resistance mechanism to lorlatinib. Lung cancer,
Vol.134,
pp. 117-120.
Popat, S.
(2019). Histologically Transformed SCLC From EGFR-Mutant NSCLC: Understanding the Wolf in Sheep’s Clothing. Journal of thoracic oncology,
Vol.14
(10),
pp. 1689-1691.
Popat, S.
(2019). Hyperprogression with immunotherapy: Is it real?. Cancer,
Vol.125
(8),
pp. 1218-1220.
Tokaca, N.
Barth, S.
O'Brien, M.
Bhosle, J.
Fotiadis, N.
Wotherspoon, A.
Thompson, L.
Popat, S.
(2018). Molecular Adequacy of Image-Guided Rebiopsies for Molecular Retesting in Advanced Non-Small Cell Lung Cancer: A Single-Center Experience. Journal of thoracic oncology : official publication of the international association for the study of lung cancer,
Vol.13
(1),
pp. 63-72.
show abstract
Introduction In the era of biomarker-driven systemic therapy for advanced NSCLC, the role of routine repeated biopsies for decision making outside EGFR-mutant disease remains unproven. We report our center's experience of safety and adequacy for molecular retesting of tumor material obtained from image-guided lung rebiopsies in NSCLC.Methods We performed a retrospective case note analysis of patients undergoing image-guided lung rebiopsies at a single cancer center between 2011 and 2014. The primary objective was to determine the pathological success rate. Secondary and exploratory objectives were to determine technical success rate, histological concordance, molecular adequacy, genotypes identified, and complication rate.Results In all, 103 patients underwent transthoracic image-guided procedures. A total of 66 rebiopsies in NSCLC were identified and analyzed. The pathological success rate was 87.1%. A high histological discordance rate was observed (12 of 52 evaluable cases [23.1%]). Pretest molecular adequacy as determined by the lung pathologist was 78.8% (52 of 66). Of 52 adequate samples 51 were sent for molecular analysis, with a total of 209 genes analyzed (including EGFR, ALK receptor tyrosine kinase gene [ALK], KRAS, BRAF, dicoidin domain receptor tyrosine kinase 2 gene [DDR2], NRAS, ROS1, and rearranged during transfection proto-oncogene gene [RET]). The rate of postgenotyping molecular adequacy was 87.1% (182 of 209). Overall, 20 new potentially actionable mutations were identified, with 13 of 66 patients (19.7%) starting to receive new targeted treatment as a result. Overall, rebiopsies informed clinical decision making in 63.6% of cases. The rates of complications were 15% for pneumothorax, 3% for pneumothorax requiring chest drain, and 8% for hemoptysis.Conclusions We have validated the pathological and molecular adequacy rates of rebiopsies and demonstrated clinical utility in routine decision making..
Melosky, B.
Popat, S.
Gandara, D.R.
(2018). An Evolving Algorithm to Select and Sequence Therapies in EGFR Mutation-positive NSCLC: A Strategic Approach. Clinical lung cancer,
Vol.19
(1),
pp. 42-50.
show abstract
The optimal treatment sequence for patients with metastatic epidermal growth factor receptor (EGFR) mutation-positive (EGFR-M + ) non-small-cell lung cancer (NSCLC) continues to evolve, related largely to an increasing number of breakthroughs and studies in the field. The efficacy of tyrosine kinase inhibitors in the treatment of these patients is well established; however, the treatment decision-making process is becoming more complex as our knowledge of EGFR mutations and resistance pathways grows and more treatment options become available. Thus, treating physicians must consider an increasing number of factors. We present a stepwise approach to personalizing the treatment of patients with EGFR-M + NSCLC, emphasizing some of the real world challenges faced by treating physicians. We reviewed the decision criteria for selecting the best first-line therapy, highlighted the importance of repeat biopsy on disease progression to determine the most appropriate next-line therapy, and discussed the options for third-line therapy and beyond. We also present an algorithm designed to optimize the sequencing strategies for prolonging survival and maintaining quality of life in our patients with EGFR-M + NSCLC..
Felip, E.
Hirsh, V.
Popat, S.
Cobo, M.
Fülöp, A.
Dayen, C.
Trigo, J.M.
Gregg, R.
Waller, C.F.
Soria, J.-.
Goss, G.D.
Gordon, J.
Wang, B.
Palmer, M.
Ehrnrooth, E.
Gadgeel, S.M.
(2018). Symptom and Quality of Life Improvement in LUX-Lung 8, an Open-Label Phase III Study of Second-Line Afatinib Versus Erlotinib in Patients With Advanced Squamous Cell Carcinoma of the Lung After First-Line Platinum-Based Chemotherapy. Clinical lung cancer,
Vol.19
(1),
pp. 74-83.e11.
show abstract
Introduction In the phase III LUX-Lung 8 trial, afatinib significantly improved progression-free survival (PFS) and overall survival (OS) versus erlotinib in patients with squamous cell carcinoma (SCC) of the lung progressing during or after platinum-based chemotherapy. Patient-reported outcomes (PROs) and health-related quality of life (QoL) in these patients are presented.Patients and methods Patients (n = 795) were randomized 1:1 to oral afatinib (40 mg/d) or erlotinib (150 mg/d). PROs were collected (baseline, every 28 days until progression, 28 days after discontinuation) using the European Organization for Research and Treatment of Cancer QoL questionnaire and lung cancer-specific module. The percentage of patients improved during therapy, time to deterioration (TTD), and changes over time were analyzed for prespecified lung cancer-related symptoms and global health status (GHS)/QoL.Results Questionnaire compliance was 77.3% to 99.0% and 68.7% to 99.0% with afatinib and erlotinib, respectively. Significantly more patients who received afatinib versus erlotinib experienced improved scores for GHS/QoL (36% vs. 28%; P = .041) and cough (43% vs. 35%; P = .029). Afatinib significantly delayed TTD in dyspnea (P = .008) versus erlotinib, but not cough (P = .256) or pain (P = .869). Changes in mean scores favored afatinib for cough (P = .0022), dyspnea (P = .0007), pain (P = .0224), GHS/QoL (P = .0320), and all functional scales. Differences in adverse events between afatinib and erlotinib, specifically diarrhea, did not affect GHS/QoL.Conclusion In patients with SCC of the lung, second-line afatinib was associated with improved prespecified disease-related symptoms and GHS/QoL versus erlotinib, complementing PFS and OS benefits with afatinib..
Califano, R.
Lal, R.
Lewanski, C.
Nicolson, M.C.
Ottensmeier, C.H.
Popat, S.
Hodgson, M.
Postmus, P.E.
(2018). Patient selection for anti-PD-1/PD-L1 therapy in advanced non-small-cell lung cancer: implications for clinical practice. Future oncology,
Vol.14
(23),
pp. 2415-2431.
show abstract
Immune checkpoint inhibitors targeting PD-1 or PD-L1 represent a standard treatment option for patients with advanced non-small-cell lung cancer. However, a substantial proportion of patients will not benefit from these treatments, and robust biomarkers are required to help clinicians select patients who are most likely to benefit. Here, we discuss the available evidence on the utility of clinical characteristics in the selection of patients with advanced non-small-cell lung cancer as potential candidates for single-agent anti-PD-1/PD-L1 therapy, and provide practical guidance to clinicians on identifying those patients who are most likely to benefit. Recommendations on the use of immune checkpoint inhibitor in clinically challenging populations are also provided. .
Curioni, A.
Felip, E.
Dafni, U.
Molina, M.-.
Gautschi, O.
Peters, S.
Massutí, B.
Palmero, R.
Ponce, S.
Carcereny, E.
Früh, M.
Pless, M.
Popat, S.
Cuffe, S.
Karachaliou, N.
Kammler, R.
Kassapian, M.
Roschitzki-Voser, H.
Stahel, R.A.
Rosell, R.
(2018). Evolution and clinical impact of EGFR mutations in circulating free DNA in the BELIEF trial. Annals of oncology,
Vol.29,
pp. viii513-viii513.
Planchard, D.
Popat, S.
Kerr, K.
Novello, S.
Smit, E.F.
Faivre-Finn, C.
Mok, T.S.
Reck, M.
Van Schil, P.E.
Hellmann, M.D.
Peters, S.
ESMO Guidelines Committee. Electronic address: [email protected],
(2018). Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of oncology : official journal of the european society for medical oncology,
Vol.29 Suppl 4,
pp. iv192-iv237.
Camidge, D.R.
Kim, H.R.
Ahn, M.-.
Yang, J.C.
Han, J.-.
Lee, J.-.
Hochmair, M.J.
Li, J.Y.
Chang, G.-.
Lee, K.H.
Gridelli, C.
Delmonte, A.
Garcia Campelo, R.
Kim, D.-.
Bearz, A.
Griesinger, F.
Morabito, A.
Felip, E.
Califano, R.
Ghosh, S.
Spira, A.
Gettinger, S.N.
Tiseo, M.
Gupta, N.
Haney, J.
Kerstein, D.
Popat, S.
(2018). Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer. The new england journal of medicine,
Vol.379
(21),
pp. 2027-2039.
show abstract
Background Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, has robust efficacy in patients with ALK-positive non-small-cell lung cancer (NSCLC) that is refractory to crizotinib. The efficacy of brigatinib, as compared with crizotinib, in patients with advanced ALK-positive NSCLC who have not previously received an ALK inhibitor is unclear.Methods In an open-label, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced ALK-positive NSCLC who had not previously received ALK inhibitors to receive brigatinib at a dose of 180 mg once daily (with a 7-day lead-in period at 90 mg) or crizotinib at a dose of 250 mg twice daily. The primary end point was progression-free survival as assessed by blinded independent central review. Secondary end points included the objective response rate and intracranial response. The first interim analysis was planned when approximately 50% of 198 expected events of disease progression or death had occurred.Results A total of 275 patients underwent randomization; 137 were assigned to brigatinib and 138 to crizotinib. At the first interim analysis (99 events), the median follow-up was 11.0 months in the brigatinib group and 9.3 months in the crizotinib group. The rate of progression-free survival was higher with brigatinib than with crizotinib (estimated 12-month progression-free survival, 67% [95% confidence interval {CI}, 56 to 75] vs. 43% [95% CI, 32 to 53]; hazard ratio for disease progression or death, 0.49 [95% CI, 0.33 to 0.74]; P<0.001 by the log-rank test). The confirmed objective response rate was 71% (95% CI, 62 to 78) with brigatinib and 60% (95% CI, 51 to 68) with crizotinib; the confirmed rate of intracranial response among patients with measurable lesions was 78% (95% CI, 52 to 94) and 29% (95% CI, 11 to 52), respectively. No new safety concerns were noted.Conclusions Among patients with ALK-positive NSCLC who had not previously received an ALK inhibitor, progression-free survival was significantly longer among patients who received brigatinib than among those who received crizotinib. (Funded by Ariad Pharmaceuticals; ALTA-1L ClinicalTrials.gov number, NCT02737501 .)..
Popat, S.
(2018). Osimertinib as First-Line Treatment in EGFR-Mutated Non–Small-Cell Lung Cancer. New england journal of medicine,
Vol.378
(2),
pp. 192-193.
Lindsay, C.R.
Shaw, E.C.
Blackhall, F.
Blyth, K.G.
Brenton, J.D.
Chaturvedi, A.
Clarke, N.
Dick, C.
Evans, T.R.
Hall, G.
Hanby, A.M.
Harrison, D.J.
Johnston, S.R.
Mason, M.D.
Morton, D.
Newton-Bishop, J.
Nicholson, A.G.
Oien, K.A.
Popat, S.
Rassl, D.
Sharpe, R.
Taniere, P.
Walker, I.
Wallace, W.A.
West, N.P.
Butler, R.
Gonzalez de Castro, D.
Griffiths, M.
Johnson, P.W.
Rehal, P.
Butler, S.
Smith, M.
Doak, R.
Tanska, A.
Halford, G.
James, L.
Kotara, C.
Masson, G.
Clokie, S.
Bell, J.
Macdonald, F.
Griffiths, M.
De Castro, D.G.
Thompson, L.
Mair, D.
Lillis, S.
Wren, D.
Hollifield, R.
Dover, K.
Maurya, M.
Brooks, D.
Gomez, B.
Grady, L.
Jones, T.
Hooper, C.
Webster, D.
Travis, J.
Ogwuru, S.
Gazdova, J.
Collins, D.
Chapman, E.
Leavey, L.
Proszek, P.
Hulkki, S.
Collins, V.P.
Ibrahim, A.
Brown, K.
Burge, J.
Burnett, K.
Devonshire, G.
Moseley, E.
Haynes, B.
Hodgkin, C.
Jimenez-linan, M.
Jones, L.
Kenyon, G.
Mahler-araujo, B.
Payne, K.
Piper, J.
Rassl, D.
Richardson, S.
Rytina, E.
Warren, A.
Coker, L.
Godsall, G.
Arends, M.
O’Neill, A.
Rintoul, K.
Goymer, D.
Taylor, J.
Matthews, C.
Bhayani, H.
Osalador, T.
Niwaz, Z.
Higgins, A.
Bamsey, O.
Salter, J.
Renouf, L.
Noel-Storr, G.
Roberts, H.
Gierejko, K.
Knapman, P.
Wotherspoon, A.
Stamp, G.
Attygailye, A.
Hazell, S.
Osin, P.
Nerurkar, A.
Francis, S.
Runde, M.
Arch, J.
Chitnis, X.
Siu, B.
Townsend, D.
Hennelly, L.
Taylor, N.
Johnson, B.
Banerjee, S.
Pyle, L.
Hamill, M.
Gyertson, J.
George, A.
Patel, K.
Pearce, K.
Edmonds, K.
Sarker, S.
Eeles, R.
Bancroft, L.
Taylor, N.
Thomas, S.
Kano, Y.
Rowland, L.
Brooks, K.
Popat, S.
O’brien, M.
Bhosle, J.
Priest, K.
Ayite, B.
Severn, J.
Beedham, H.
Lucas, N.
Tye, K.
Lorentzos, A.
Webb, J.
Kerr, S.
Corestav, L.
Bottero, D.
Jell, L.
Thomas, J.
Marriott, C.
Rajah, N.
Cole, A.
Ly, D.
Taniere, P.
O’sullivan, B.
Swift, C.
Hughes, F.
Neil, D.
Hanby, A.
Banks, R.
Ajayi, D.
Barclay, A.
Bishop, J.N.
Beirne, D.
Bernard, A.
Berry, M.
Bentley, J.
Bishop, T.
Chambers, A.
Clarke, J.
Crossley, A.
Gahir, N.
Gibson, D.
Good, R.
Grosios, K.
Hall, G.
Harnden, P.
Hasler, K.
Hindmarch, D.
Jackson, S.
Johnstone, C.
Jones, A.-.
Lambert, G.
Lane, S.
Mcnicholas, N.
Millican-Slater, R.
Moriaty, C.
Newsham, A.
O’connell, K.
Ripley, L.
Sebag-Montefiore, D.
Simpson, M.
Speirs, V.
Sugden, J.
Tate, L.
Tidswell, E.
Twelves, C.
Walker, C.
Waterhouse, B.
Waugh, M.
White, L.
Wright, E.
Rogan, J.
Ashton, G.
Abbey, C.
Greenhalgh, M.
Nonaka, D.
Shing, E.
Gibbard, C.
Burton, G.
Fawkes, N.
Marsden, A.
Waddington, R.
Harrison, P.
Moghadam, S.
Murray, K.
Brown, S.
Mitchinson, C.
Booton, R.
Shah, R.
Blackhall, F.
Clarke, N.
Harrison, D.
Oniscu, A.
Wallace, W.
Rae, F.
Marshall, C.
Mcleod, L.
Charles, M.
Sutherland, S.J.
Dawson, C.
Mitchell, P.
Maclellan, A.
Muir, S.
Johnstone, L.
O’connor, J.
Johnstone, S.
Mcpherson, J.
Hair, J.
Pignatelli, M.
Armstrong, R.
Oien, K.
Evans, J.
Burgoyne, M.
Blessing, K.
Duthie, F.
Moyes, C.
Mallon, E.
Millan, D.
Roberts, F.
Seywright, M.
Fraser, S.
Dick, C.
Ford, I.
Kean, S.
Flood, M.
Grant, D.
Mcdonald, C.
Moffat, T.
Mclelland, H.
Kyle, A.
Cameron, G.
Wright, M.
Kenny, S.
Mcauslan, K.
Jones, A.
Fitzsimons, T.
Graham, F.
Bell, A.
Duffy, P.
Fisher, A.
Smith, A.
Shannon, E.
Woods, B.
Hutchison, C.
Booth, A.
Duffy, L.
Mcculloch, G.
Sadiq, H.
Deakin, S.
Haywood, S.
Mason, M.
Chester, J.
Parry-jones, A.
Macarthur, A.
Williams, S.
Griffiths, D.
Morgan, F.
Bailey, H.
(2018). Somatic cancer genetics in the UK: real-world data from phase I of the Cancer Research UK Stratified Medicine Programme. Esmo open,
Vol.3
(6),
pp. e000408-e000408.
Minchom, A.
Thavasu, P.
Ahmad, Z.
Stewart, A.
Georgiou, A.
O'Brien, M.E.
Popat, S.
Bhosle, J.
Yap, T.A.
de Bono, J.
Banerji, U.
(2017). A study of PD-L1 expression in KRAS mutant non-small cell lung cancer cell lines exposed to relevant targeted treatments. Plos one,
Vol.12
(10),
pp. e0186106-?.
show abstract
We investigated PD-L1 changes in response to MEK and AKT inhibitors in KRAS mutant lung adenocarcinoma (adeno-NSCLC). PD-L1 expression was quantified using immunofluorescence and co-culture with a jurkat cell-line transfected with NFAT-luciferase was used to study if changes in PD-L1 expression in cancer cell lines were functionally relevant. Five KRAS mutant cell lines with high PD-L1 expression (H441, H2291, H23, H2030 and A549) were exposed to GI50 inhibitor concentrations of a MEK inhibitor (trametinib) and an AKT inhibitor (AZD5363) for 3 weeks. Only 3/5 (H23, H2030 and A549) and 2/5 cell lines (H441 and H23) showed functionally significant increases in PD-L1 expression when exposed to trametinib or AZD5363 respectively. PD-L1 overexpression is not consistent and is unlikely to be an early mechanism of resistance to KRAS mutant adeno-NSCLC treated with MEK or AKT inhibitors..
Yap, T.A.
Macklin-Doherty, A.
Popat, S.
(2017). Continuing EGFR inhibition beyond progression in advanced non-small cell lung cancer. European journal of cancer (oxford, england : 1990),
Vol.70,
pp. 12-21.
show abstract
The majority of patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) respond to first-line EGFR tyrosine kinase inhibitors (TKIs), but nearly all inevitably acquire resistance and develop disease progression. Conventional practice would be to switch treatments to second-line therapy. However, continuing TKIs beyond progression is becoming increasingly commonplace in patients with indolent, small volume asymptomatic growth, who may potentially continue to derive ongoing clinical benefit and to avoid a 'withdrawal tumour flare'. Nevertheless, there are limitations to our current criteria for assessing disease response, which are based on radiological assessments without considering symptomatic benefit, or the complex molecular and clinical heterogeneity of tumour growth and drug response patterns. In this article, we review the rationale for continuing EGFR inhibitors in patients with EGFR mutant NSCLC beyond disease progression and discuss strategies that have been pursued in the context of molecularly and clinically heterogeneous populations of tumour growth depending on the different clinical scenarios encountered. We discuss the management of systemic disease progression, including continuing EGFR TKIs alone, introducing a drug holiday, or combining TKIs with chemotherapy or other molecularly targeted agents. We also focus on approaches in managing patients with indolent, small volume asymptomatic growth (non-CNS oligometastatic disease progression) and those with oligometastatic EGFR mutant NSCLC with involvement of the central nervous system. We envision future precision medicine strategies through the use of next generation sequencing strategies of serial tumour rebiopsies and circulating plasma DNA to individualise the management for such patients during disease progression..
Yap, T.A.
Popat, S.
(2017). Targeting MET Exon 14 Skipping Alterations: Has Lung Cancer MET Its Match?. Journal of thoracic oncology : official publication of the international association for the study of lung cancer,
Vol.12
(1),
pp. 12-14.
Juan, O.
Yousaf, N.
Popat, S.
(2017). First-line Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors for EGFR Mutant Non-small Cell Lung Cancer: And the Winner is…. Clinical oncology (royal college of radiologists (great britain)),
Vol.29
(1),
pp. e1-e4.
Juan, O.
Popat, S.
(2017). Crizotinib for ROS1 patients: One small step in biomarker testing, one giant leap for advanced NSCLC patients. Lung cancer (amsterdam, netherlands),
Vol.104,
pp. 131-133.
Juan, O.
Popat, S.
(2017). Treatment choice in epidermal growth factor receptor mutation-positive non-small cell lung carcinoma: latest evidence and clinical implications. Therapeutic advances in medical oncology,
Vol.9
(3),
pp. 201-216.
show abstract
Discovery of sensitizing mutations in epidermal growth factor receptor ( EGFR) and the subsequent development of EGFR tyrosine kinase inhibitors (TKIs) have substantially changed the treatment of lung cancer. First-line treatment with EGFR TKIs (gefitinib, erlotinib and afatinib) has demonstrated a superior response rate and progression-free survival (PFS) compared with chemotherapy in EGFR -mutation positive patients. However, a number of open questions remain, such as choice between the three EGFR TKIs licensed, treatment of patients unsuitable for chemotherapy due to morbidity or advanced age, management of acquired resistance and optimal biological sample to determine EGFR status. Recently the first head-to-head trial comparing gefitinib and afatinib (LUX-Lung 7) has been reported. Moreover, third-generation EGFR TKIs such as osimertinib, rociletinib, olmutinib and ASP8273, with preferential activity against T790M mutant tumours, the commonest resistance mechanism to EGFR TKIs, have shown promising results in early clinical trials, with osimertinib now licensed. In this review, we summarize latest advances in the treatment of EGFR -mutation positive patients focusing on controversial areas and emerging challenges to optimally treat these patients in the future..
Papadatos-Pastos, D.
Roda, D.
De Miguel Luken, M.J.
Petruckevitch, A.
Jalil, A.
Capelan, M.
Michalarea, V.
Lima, J.
Diamantis, N.
Bhosle, J.
Molife, L.R.
Banerji, U.
de Bono, J.S.
Popat, S.
O'Brien, M.E.
Yap, T.A.
(2017). Clinical outcomes and prognostic factors of patients with advanced mesothelioma treated in a phase I clinical trials unit. European journal of cancer (oxford, england : 1990),
Vol.75,
pp. 56-62.
show abstract
Background We have previously reported a prognostic score for patients in phase I trials in the Drug Development Unit, treated at the Royal Marsden Hospital (RPS). The RPS is an objective tool used in patient selection for phase I trials based on albumin, number of disease sites and LDH. Patients with mesothelioma are often selected for phase I trials as the disease remains localised for long periods of time. We have now reviewed the clinical outcomes of patients with relapsed malignant mesothelioma (MM) and propose a specific mesothelioma prognostic score (m-RPS) that can help identify patients who are most likely to benefit from early referral.Methods Patients who participated in 38 phase I trials between September 2003 and November 2015 were included in the analysis. Efficacy was assessed by response rate, median overall survival (OS) and progression-free survival (PFS). Univariate (UVA) and multivariate analyses (MVA) were carried out to develop the m-RPS.Results A total of 65 patients with advanced MM were included in this retrospective study. The PFS was 2.5 months (95% confidence interval [CI] 2.0-3.1 months) and OS was 8 months (95% CI 5.6-9.8 months). A total of four (6%) patients had RECIST partial responses, whereas 26 (40%) patients had RECIST stable disease >3 months. The m-RPS was developed comprising of three different prognostic factors: a neutrophil: lymphocyte ratio greater than 3, the presence of more than two disease sites (including lymph nodes as a single site of disease) and albumin levels less than 35 from the MVA. Patients each received a score of 1 for the presence of each factor. Patients in group A (m-RPS 0-1; n = 35) had a median OS of 13.4 months (95% CI 8.5-21.6), whereas those in group B (m-RPS 2-3; n = 30) had a median OS of 4.0 months (95% CI 2.9-7.1, P < 0.0001). A total of 56 (86%) patients experienced G1-2 toxicities, whereas reversible G3-4 toxicities were observed in 18 (28%) patients. Only 10 (15%) patients discontinued phase I trials due to toxicity.Conclusions Phase I clinical trial therapies were well tolerated with early signals of antitumour activity in advanced MM patients. The m-RPS is a useful tool to assess MM patient suitability for phase I trials and should now be prospectively validated..
Dolly, S.O.
Collins, D.C.
Sundar, R.
Popat, S.
Yap, T.A.
(2017). Advances in the Development of Molecularly Targeted Agents in Non-Small-Cell Lung Cancer. Drugs,
Vol.77
(8),
pp. 813-827.
show abstract
Non-small-cell lung cancer (NSCLC) remains a significant global health challenge and the leading cause of cancer-related mortality. The traditional 'one-size-fits-all' treatment approach has now evolved into one that involves personalized strategies based on histological and molecular subtypes. The molecular era has revolutionized the treatment of patients harboring epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and ROS1 gene aberrations. In the appropriately selected population, anti-tumor agents against these molecular targets can significantly improve progression-free survival. However, the emergence of acquired resistance is inevitable. Novel potent compounds with much improved and rational selectivity profiles, such as third-generation EGFR T790M resistance mutation-specific inhibitors, have been developed and added to the NSCLC armamentarium. To date, attempts to overcome resistance bypass pathways through downstream signaling blockade has had limited success. Furthermore, the majority of patients still do not harbor known driver genetic or epigenetic alterations and/or have no new available treatment options, with chemotherapy remaining their standard of care. Several potentially actionable driver aberrations have recently been identified, with the early clinical development of multiple inhibitors against these promising targets currently in progress. The advent of immune checkpoint inhibitors has led to significant benefit for advanced NSCLC patients with durable responses observed. Further interrogation of the underlying biology of NSCLC, coupled with modern clinical trial designs, is now required to develop novel targeted therapeutics rationally matched with predictive biomarkers of response, so as to further advance NSCLC therapeutics through the next decade..
Popat, S.
(2017). Do Statins Improve Survival in Small-Cell Lung Cancer?. Journal of clinical oncology : official journal of the american society of clinical oncology,
Vol.35
(14),
pp. 1497-1498.
Rosell, R.
Dafni, U.
Felip, E.
Curioni-Fontecedro, A.
Gautschi, O.
Peters, S.
Massutí, B.
Palmero, R.
Aix, S.P.
Carcereny, E.
Früh, M.
Pless, M.
Popat, S.
Kotsakis, A.
Cuffe, S.
Bidoli, P.
Favaretto, A.
Froesch, P.
Reguart, N.
Puente, J.
Coate, L.
Barlesi, F.
Rauch, D.
Thomas, M.
Camps, C.
Gómez-Codina, J.
Majem, M.
Porta, R.
Shah, R.
Hanrahan, E.
Kammler, R.
Ruepp, B.
Rabaglio, M.
Kassapian, M.
Karachaliou, N.
Tam, R.
Shames, D.S.
Molina-Vila, M.A.
Stahel, R.A.
BELIEF collaborative group,
(2017). Erlotinib and bevacizumab in patients with advanced non-small-cell lung cancer and activating EGFR mutations (BELIEF): an international, multicentre, single-arm, phase 2 trial. The lancet. respiratory medicine,
Vol.5
(5),
pp. 435-444.
show abstract
Background The tyrosine kinase inhibitor erlotinib improves the outcomes of patients with advanced non-small-cell lung carcinoma (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations. The coexistence of the T790M resistance mutation with another EGFR mutation in treatment-naive patients has been associated with a shorter progression-free survival to EGFR inhibition than in the absence of the T790M mutation. To test this hypothesis clinically, we developed a proof-of-concept study, in which patients with EGFR-mutant NSCLC were treated with the combination of erlotinib and bevacizumab, stratified by the presence of the pretreatment T790M mutation.Methods BELIEF was an international, multicentre, single-arm, phase 2 trial done at 29 centres in eight European countries. Eligible patients were aged 18 years or older and had treatment-naive, pathologically confirmed stage IIIB or stage IV lung adenocarcinoma with a confirmed, activating EGFR mutation (exon 19 deletion or L858R mutation). Patients received oral erlotinib 150 mg per day and intravenous bevacizumab 15 mg/kg every 21 days and were tested centrally for the pretreatment T790M resistance mutation with a peptide nucleic acid probe-based real-time PCR. The primary endpoint was progression-free survival. The primary efficacy analysis was done in the intention-to-treat population and was stratified into two parallel substudies according to the centrally confirmed pretreatment T790M mutation status of enrolled patients (T790M positive or negative). The safety analysis was done in all patients that have received at least one dose of trial treatment. This trial was registered with ClinicalTrials.gov, number NCT01562028.Findings Between June 11, 2012, and Oct 28, 2014, 109 patients were enrolled and included in the efficacy analysis. 37 patients were T790M mutation positive and 72 negative. The overall median progression-free survival was 13·2 months (95% CI 10·3-15·5), with a 12 month progression-free survival of 55% (95% CI 45-64). The primary endpoint was met only in substudy one (T790M-positive patients). In the T790M-positive group, median progression-free survival was 16·0 months (12·7 to not estimable), with a 12 month progression-free survival of 68% (50-81), whereas in the T790M-negative group, median progression-free survival was 10·5 months (9·4-14·2), with a 12 month progression-free survival of 48% (36-59). Of 106 patients included in the safety analysis, five had grade 4 adverse events (one acute coronary syndrome, one biliary tract infection, one other neoplasms, and two colonic perforations) and one died due to sepsis.Interpretation The BELIEF trial provides further evidence of benefit for the combined use of erlotinib and bevacizumab in patients with NSCLC harbouring activating EGFR mutations.Funding European Thoracic Oncology Platform, Roche..
Gautschi, O.
Milia, J.
Filleron, T.
Wolf, J.
Carbone, D.P.
Owen, D.
Camidge, R.
Narayanan, V.
Doebele, R.C.
Besse, B.
Remon-Masip, J.
Janne, P.A.
Awad, M.M.
Peled, N.
Byoung, C.-.
Karp, D.D.
Van Den Heuvel, M.
Wakelee, H.A.
Neal, J.W.
Mok, T.S.
Yang, J.C.
Ou, S.-.
Pall, G.
Froesch, P.
Zalcman, G.
Gandara, D.R.
Riess, J.W.
Velcheti, V.
Zeidler, K.
Diebold, J.
Früh, M.
Michels, S.
Monnet, I.
Popat, S.
Rosell, R.
Karachaliou, N.
Rothschild, S.I.
Shih, J.-.
Warth, A.
Muley, T.
Cabillic, F.
Mazières, J.
Drilon, A.
(2017). Targeting RET in Patients With RET-Rearranged Lung Cancers: Results From the Global, Multicenter RET Registry. Journal of clinical oncology : official journal of the american society of clinical oncology,
Vol.35
(13),
pp. 1403-1410.
show abstract
Purpose In addition to prospective trials for non-small-cell lung cancers (NSCLCs) that are driven by less common genomic alterations, registries provide complementary information on patient response to targeted therapies. Here, we present the results of an international registry of patients with RET-rearranged NSCLCs, providing the largest data set, to our knowledge, on outcomes of RET-directed therapy thus far. Methods A global, multicenter network of thoracic oncologists identified patients with pathologically confirmed NSCLC that harbored a RET rearrangement. Molecular profiling was performed locally by reverse transcriptase polymerase chain reaction, fluorescence in situ hybridization, or next-generation sequencing. Anonymized data-clinical, pathologic, and molecular features-were collected centrally and analyzed by an independent statistician. Best response to RET tyrosine kinase inhibition administered outside of a clinical trial was determined by RECIST v1.1. Results By April 2016, 165 patients with RET-rearranged NSCLC from 29 centers across Europe, Asia, and the United States were accrued. Median age was 61 years (range, 29 to 89 years). The majority of patients were never smokers (63%) with lung adenocarcinomas (98%) and advanced disease (91%). The most frequent rearrangement was KIF5B-RET (72%). Of those patients, 53 received one or more RET tyrosine kinase inhibitors in sequence: cabozantinib (21 patients), vandetanib (11 patients), sunitinib (10 patients), sorafenib (two patients), alectinib (two patients), lenvatinib (two patients), nintedanib (two patients), ponatinib (two patients), and regorafenib (one patient). The rate of any complete or partial response to cabozantinib, vandetanib, and sunitinib was 37%, 18%, and 22%, respectively. Further responses were observed with lenvantinib and nintedanib. Median progression-free survival was 2.3 months (95% CI, 1.6 to 5.0 months), and median overall survival was 6.8 months (95% CI, 3.9 to 14.3 months). Conclusion Available multikinase inhibitors had limited activity in patients with RET-rearranged NSCLC in this retrospective study. Further investigation of the biology of RET-rearranged lung cancers and identification of new targeted therapeutics will be required to improve outcomes for these patients..
Popat, S.
Mellemgaard, A.
Reck, M.
Hastedt, C.
Griebsch, I.
(2017). Nintedanib plus docetaxel as second-line therapy in patients with non-small-cell lung cancer of adenocarcinoma histology: a network meta-analysis vs new therapeutic options. Future oncology (london, england),
Vol.13
(13),
pp. 1159-1171.
show abstract
Patients & methods We provide an update to a network meta-analysis evaluating the relative efficacy of nintedanib + docetaxel versus other second-line agents in adenocarcinoma histology non-small-cell lung cancer.Results Overall similarity of nintedanib + docetaxel versus ramucirumab + docetaxel, and versus nivolumab. Comparing nintedanib + docetaxel with nivolumab, hazards ratio (HR) of overall survival and progression-free survival (PFS) pointed in opposite directions (overall survival: HR: 1.20 [95% credible interval: 0.92-1.58]; PFS: HR: 0.91 [0.68-1.21]). Exploratory subgroup analysis indicated superiority of nivolumab in high PD-L1 expression level subgroups; results were more favorable for nintedanib in all subgroups with low (<1%, <5%, <10%) PD-L1 expression levels - in particular, with regard to PFS.Conclusion Results demonstrated similar efficacy of nintedanib + docetaxel compared with the new therapeutic options ramucirumab + docetaxel and nivolumab, with potential differences in subgroups according to PD-L1 expression level..
Yap, T.A.
Aerts, J.G.
Popat, S.
Fennell, D.A.
(2017). Novel insights into mesothelioma biology and implications for therapy. Nature reviews. cancer,
Vol.17
(8),
pp. 475-488.
show abstract
Malignant mesothelioma is a universally lethal cancer that is increasing in incidence worldwide. There is a dearth of effective therapies, with only one treatment (pemetrexed and cisplatin combination chemotherapy) approved in the past 13 years. However, the past 5 years have witnessed an exponential growth in our understanding of mesothelioma pathobiology, which is set to revolutionize therapeutic strategies. From a genomic standpoint, mesothelioma is characterized by a preponderance of tumour suppressor alterations, for which novel therapies are currently in development. Other promising antitumour agents include inhibitors against angiogenesis, mesothelin and immune checkpoints, which are at various phases of clinical trial testing..
Nimako, K.
Ayite, B.
Priest, K.
Severn, J.
Fries, H.M.
Gunapala, R.
Bhosle, J.
Popat, S.
O'Brien, M.
(2017). A randomised assessment of the use of a quality of life questionnaire with or without intervention in patients attending a thoracic cancer clinic. European journal of cancer care,
Vol.26
(4).
show abstract
The study examined the impact of using a quality of life (QoL) questionnaire during a clinic to identify QoL issues and to improve QoL. 138 patients were randomised (1:1:1) to either (1) an Intervention group that completed the European Organisation for Research and Treatment of Cancer-Core Quality of Life Questionnaire and Lung Cancer Module (EORTC QLQ-C30 and LC13) at baseline and received feedback during a clinic, (2) an Attention group that completed the questionnaire at baseline without feedback and (3) a Control group that did not complete the questionnaire. All patients completed the same questionnaire 6 weeks later and a contact diary during the study period. There was a significant difference between the Intervention and Control groups for the mean number of QoL issues identified at baseline (4.69 vs. 2.81, P = 0.006) and the mean number of actions taken (4.41 vs. 2.46, P = 0.004). At 6 weeks, there was no difference between the groups in global QoL (Intervention vs. Control group, P = 0.596; Attention vs. Control, P = 0.973). The results suggest that the completion of the EORTC QLQ-C30 LC13 with feedback improves communication and increases the number of QoL issues identified and actions taken. However, the intervention does not impact on QoL per se. Clinicaltrials.gov: NCT01213745..
Capelan, M.
Roda, D.
Geuna, E.
Rihawi, K.
Bodla, S.
Kaye, S.B.
Bhosle, J.
Banerji, U.
O'Brien, M.
de Bono, J.S.
Popat, S.
Yap, T.A.
(2017). Phase I clinical trials in patients with advanced non-small cell lung cancer treated within a Drug Development Unit: What have we learnt?. Lung cancer (amsterdam, netherlands),
Vol.111,
pp. 6-11.
show abstract
Objectives Despite advances in novel drug development for patients with advanced non-small cell lung cancer (NSCLC), there are still only a limited number of approved treatments. We therefore evaluated the clinical outcomes of patients with advanced NSCLC referred to a dedicated phase I clinical trials unit assessed baseline clinical factors associated with successful enrollment onto phase I trials.Material and methods We conducted a retrospective study involving patients with advanced NSCLC referred to the Drug Development Unit at the RMH between January 2005 and December 2013.Results 257 patients with advanced NSCLC were referred for consideration of phase I trials, of which only 89 (35%) patients successfully commenced phase I trials. The commonest reasons for not entering study included poor ECOG performance status and rapid disease progression. A multivariate analysis identified that ECOG performance status (0-1) and RMH prognostic score (0-1) were associated with successful enrollment onto phase I trials (p<0.001). Single agent therapies included novel agents against the phosphatidylinositol-3 kinase pathway, insulin growth factor-1 receptor and pan-HER family tyrosine kinases. These trial therapies were well tolerated and mainly associated with grade 1-2 adverse events, with a minority experiencing grade 3 toxicities. Nine (10%) patients, 4 with known EGFR or KRAS mutations, achieved RECIST partial responses. Median time to progression was 2.6 months and median overall survival was 8.1 months for patients enrolled.Conclusions Phase I trial therapies were generally well tolerated with potential antitumor benefit for patients with advanced NSCLC. Early referral to drug development units at time of disease progression should be considered to enhance the odds of patient participation in these studies..
Yousaf, N.
Popat, S.
(2017). Endocrine manifestations of malignancy. Medicine,
Vol.45
(9),
pp. 547-550.
Tokaca, N.
Wotherspoon, A.
Nicholson, A.G.
Fotiadis, N.
Thompson, L.
Popat, S.
(2017). Lack of response to nivolumab in a patient with EGFR-mutant non-small cell lung cancer adenocarcinoma sub-type transformed to small cell lung cancer. Lung cancer (amsterdam, netherlands),
Vol.111,
pp. 65-68.
show abstract
Small cell transformation is a rare but well recognised mechanism of acquired resistance to EGFR-TKI therapy in EGFR-mutated NSCLC, but optimal drug therapy thereof is unknown. Nivolumab has demonstrated activity in relapsed de novo small cell lung cancer in early phase trials. Here, we report a case of transformed EGFR-mutant SCLC treated with nivolumab with no benefit..
Califano, R.
Greystoke, A.
Lal, R.
Thompson, J.
Popat, S.
(2017). Management of ceritinib therapy and adverse events in patients with ALK-rearranged non-small cell lung cancer. Lung cancer (amsterdam, netherlands),
Vol.111,
pp. 51-58.
show abstract
Anaplastic lymphoma kinase rearrangement (ALK+) occurs in approximately 2-7% of patients with non-small cell lung cancer (NSCLC), contributing to a considerable number of patients with ALK+ NSCLC worldwide. Ceritinib is a next generation ALK inhibitor (ALKi), approved by the European Medicines Agency in 2015. In the first-in-human, phase I study, ceritinib demonstrated rapid and durable responses in ALK patients previously treated with a different ALKi and in those who were ALKi-naive. As ceritinib is starting to be used routinely for the treatment of patients with ALK+ NSCLC, experience is growing with regard to ideal therapy management. In this review we provide a brief background to the development of ceritinib. The optimal treatment management and adverse events associated with ceritinib in clinical trials and in clinical practice are then discussed in detail, and where applicable, an expert consensus on specific recommendations are made. In clinical trials, the most common adverse events related to ceritinib are nausea, vomiting, and diarrhea. However, the majority of these are mild and, in the opinion of the authors, can be effectively managed with dose modifications. Based on clinical data, ceritinib has demonstrated efficacy as a first-line therapy and in patients who have relapsed on crizotinib, including those with brain metastases at baseline. Unfortunately, at some point, all patients experience progressive disease, with the central nervous system being a common site of metastases. Recommendations are made for continuing treatment beyond disease progression as long as a clinical benefit to patients is observed. Here, we review management of ceritinib treatment and adverse events and make recommendations on optimal management of patients..
Scagliotti, G.V.
Gaafar, R.
Nowak, A.K.
Reck, M.
Tsao, A.S.
van Meerbeeck, J.
Vogelzang, N.J.
Nakano, T.
von Wangenheim, U.
Velema, D.
Morsli, N.
Popat, S.
(2017). LUME-Meso: Design and Rationale of the Phase III Part of a Placebo-Controlled Study of Nintedanib and Pemetrexed/Cisplatin Followed by Maintenance Nintedanib in Patients With Unresectable Malignant Pleural Mesothelioma. Clinical lung cancer,
Vol.18
(5),
pp. 589-593.
show abstract
Malignant pleural mesothelioma (MPM) is a rare but aggressive disease: median survival is 6 to 9 months if untreated. Standard first-line treatment for patients with unresectable MPM is cisplatin/pemetrexed, with a median overall survival (OS) of approximately 1 year. Improvements in first-line treatment options are needed. With the benefit of combining bevacizumab with standard therapy shown in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS), vascular endothelial growth factor (VEGF) pathway inhibition has gained renewed interest as a treatment approach. Nintedanib is an oral angiokinase inhibitor targeting multiple signaling pathways implicated in the pathogenesis of MPM, including the VEGF receptor. The phase III part of the international, phase II/III LUME-Meso study is evaluating the efficacy and safety of nintedanib plus pemetrexed/cisplatin in patients with unresectable epithelioid MPM. Originally, this was a double-blind, randomized, phase II exploratory study and was amended to include a confirmatory phase III part following the recommendation of an internal Data Monitoring Committee and review of phase II data. The phase III part plans to enroll 450 chemotherapy-naive patients, who will be randomized to receive pemetrexed/cisplatin on day 1 and nintedanib or placebo on days 2 to 21, for a maximum of 6 cycles. Patients without disease progression who are eligible to continue study treatment will receive maintenance treatment with nintedanib or placebo until disease progression or undue toxicity. The primary end point is progression-free survival; OS is the key secondary end point. The study will use an adaptive design, including an interim analysis to reassess the number of OS events required to ensure sufficient power for OS analysis. The study is currently enrolling patients..
Yang, J.C.
Ou, S.-.
De Petris, L.
Gadgeel, S.
Gandhi, L.
Kim, D.-.
Barlesi, F.
Govindan, R.
Dingemans, A.-.
Crino, L.
Lena, H.
Popat, S.
Ahn, J.S.
Dansin, E.
Golding, S.
Bordogna, W.
Balas, B.
Morcos, P.N.
Zeaiter, A.
Shaw, A.T.
(2017). Pooled Systemic Efficacy and Safety Data from the Pivotal Phase II Studies (NP28673 and NP28761) of Alectinib in ALK-positive Non-Small Cell Lung Cancer. Journal of thoracic oncology : official publication of the international association for the study of lung cancer,
Vol.12
(10),
pp. 1552-1560.
show abstract
Introduction Alectinib demonstrated clinical efficacy and an acceptable safety profile in two phase II studies (NP28761 and NP28673). Here we report the pooled efficacy and safety data after 15 and 18 months more follow-up than in the respective primary analyses.Methods Enrolled patients had ALK receptor tyrosine kinase gene (ALK)-positive NSCLC and had progressed while taking, or could not tolerate, crizotinib. Patients received oral alectinib, 600 mg twice daily. The primary end point in both studies was objective response rate assessed by an independent review committee (IRC) using the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included disease control rate, duration of response, progression-free survival, overall survival, and safety.Results The pooled data set included 225 patients (n = 138 in NP28673 and n = 87 in NP28761). The response-evaluable population included 189 patients (84% [n = 122 in NP28673 and n = 67 in NP28761]). In the response-evaluable population, objective response rate as assessed by the IRC was 51.3% (95% confidence interval [CI]: 44.0-58.6 [all PRs]), the disease control rate was 78.8% (95% CI: 72.3-84.4), and the median duration of response was 14.9 months (95% CI: 11.1-20.4) after 58% of events. Median progression-free survival as assessed by the IRC was 8.3 months (95% CI: 7.0-11.3) and median overall survival was 26.0 months (95% CI: 21.4-not estimable). Grade 3 or higher adverse events (AEs) occurred in 40% of patients, 6% of patients had treatment withdrawn on account of AEs, and 33% had AEs leading to dose interruptions/modification.Conclusions This pooled data analysis confirmed the robust systemic efficacy of alectinib in ALK-positive NSCLC with a durable response rate. Alectinib also had an acceptable safety profile with a longer duration of follow-up..
Grosso, F.
Steele, N.
Novello, S.
Nowak, A.K.
Popat, S.
Greillier, L.
John, T.
Leighl, N.B.
Reck, M.
Taylor, P.
Planchard, D.
Sørensen, J.B.
Socinski, M.A.
von Wangenheim, U.
Loembé, A.B.
Barrueco, J.
Morsli, N.
Scagliotti, G.
(2017). Nintedanib Plus Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma: Phase II Results From the Randomized, Placebo-Controlled LUME-Meso Trial. Journal of clinical oncology : official journal of the american society of clinical oncology,
Vol.35
(31),
pp. 3591-3600.
show abstract
Purpose LUME-Meso is a phase II/III randomized, double-blind trial designed to assess efficacy and safety of nintedanib plus chemotherapy as first-line treatment of malignant pleural mesothelioma (MPM). Phase II results are reported here. Patients and Methods Chemotherapy-naïve patients with unresectable, nonsarcomatoid MPM (Eastern Cooperative Oncology Group performance status 0 to 1), stratified by histology (epithelioid or biphasic), were randomly assigned in a 1:1 ratio to up to six cycles of pemetrexed and cisplatin plus nintedanib (200 mg twice daily) or placebo followed by nintedanib plus placebo monotherapy until progression. The primary end point was progression-free survival (PFS). Results Eighty-seven patients were randomly assigned. The median number of pemetrexed and cisplatin cycles was six; the median treatment duration for nintedanib was 7.8 months and 5.3 months for placebo. Primary PFS favored nintedanib (hazard ratio [HR], 0.56; 95% CI, 0.34 to 0.91; P = .017), which was confirmed in updated PFS analyses (HR, 0.54; 95% CI, 0.33 to 0.87; P = .010). A trend toward improved overall survival also favored nintedanib (HR, 0.77; 95% CI, 0.46 to 1.29; P = .319). Benefit was evident in epithelioid histology, with a median overall survival gain of 5.4 months (HR, 0.70; 95% CI, 0.40 to 1.21; P = .197; median [nintedanib v placebo], 20.6 months v 15.2 months) and median PFS gain of 4.0 months (HR, 0.49; 95% CI, 0.30 to 0.82; P = .006; median [nintedanib v placebo], 9.7 v 5.7 months). Neutropenia was the most frequent grade ≥ 3 adverse event (AE; nintedanib 43.2% v placebo 12.2%); rates of febrile neutropenia were low (4.5% in nintedanib group v 0% in placebo group). AEs leading to discontinuation were reported in 6.8% of those receiving nintedanib versus 17.1% of those in the placebo group. Conclusion Addition of nintedanib to pemetrexed plus cisplatin resulted in PFS improvement. AEs were manageable. The clinical benefit was evident in patients with epithelioid histology. The confirmatory phase III part of the study is ongoing..
Juan, O.
Popat, S.
(2017). Ablative Therapy for Oligometastatic Non-Small Cell Lung Cancer. Clinical lung cancer,
Vol.18
(6),
pp. 595-606.
show abstract
The oligometastatic state represents a distinct entity among those with metastatic disease and consists of patients with metastases limited in number and location, representing an intermediate state between locally confined and widely metastatic cancer. Although similar, "oligorecurrence" (limited number of metachronous metastases under conditions of a controlled primary lesion) and "oligoprogressive" (disease progression at a limited number of sites with disease controlled at other disease sites) states are distinct entities. In non-small cell lung cancer (NSCLC), the oligometastatic state is relatively common, with 20% to 50% of patients having oligometastatic disease at diagnosis. This subgroup of patients when receiving ablative therapy, such as surgery or stereotactic body radiation radiotherapy, can obtain markedly long progression-free and overall survival. The role of radical treatment for intracranial oligometastases is well established. Fewer data exist regarding radical treatment of extracranial metastases in lung cancer; however, retrospective series using surgery or stereotactic body radiotherapy for extracranial oligometastatic disease in NSCLC have shown excellent local control, with a suggestion of improvement in progression-free survival. In the present report, we have reviewed the data on the treatment of brain metastases in oligometastatic NSCLC and the results of ablative treatment of extracranial sites. Recently, the first randomized trial comparing ablative treatment versus control in oligometastatic disease was reported, and those data are reviewed in the context of smaller series. Finally, areas of controversy are discussed and a therapeutic approach for patients with oligometastatic disease is proposed..
Crabb, S.J.
Martin, K.
Abab, J.
Ratcliffe, I.
Thornton, R.
Lineton, B.
Ellis, M.
Moody, R.
Stanton, L.
Galanopoulou, A.
Maishman, T.
Geldart, T.
Bayne, M.
Davies, J.
Lamb, C.
Popat, S.
Joffe, J.K.
Nutting, C.
Chester, J.
Hartley, A.
Thomas, G.
Ottensmeier, C.
Huddart, R.
King, E.
(2017). COAST (Cisplatin ototoxicity attenuated by aspirin trial): A phase II double-blind, randomised controlled trial to establish if aspirin reduces cisplatin induced hearing-loss. European journal of cancer (oxford, england : 1990),
Vol.87,
pp. 75-83.
show abstract
Background Cisplatin is one of the most ototoxic chemotherapy drugs, resulting in a permanent and irreversible hearing loss in up to 50% of patients. Cisplatin and gentamicin are thought to damage hearing through a common mechanism, involving reactive oxygen species in the inner ear. Aspirin has been shown to minimise gentamicin-induced ototoxicity. We, therefore, tested the hypothesis that aspirin could also reduce ototoxicity from cisplatin-based chemotherapy.Methods A total of 94 patients receiving cisplatin-based chemotherapy for multiple cancer types were recruited into a phase II, double-blind, placebo-controlled trial and randomised in a ratio of 1:1 to receive aspirin 975 mg tid and omeprazole 20 mg od, or matched placebos from the day before, to 2 days after, their cisplatin dose(s), for each treatment cycle. Patients underwent pure tone audiometry before and at 7 and 90 days after their final cisplatin dose. The primary end-point was combined hearing loss (cHL), the summed hearing loss at 6 kHz and 8 kHz, in both ears.Results Although aspirin was well tolerated, it did not protect hearing in patients receiving cisplatin (p-value = 0.233, 20% one-sided level of significance). In the aspirin arm, patients demonstrated mean cHL of 49 dB (standard deviation [SD] 61.41) following cisplatin compared with placebo patients who demonstrated mean cHL of 36 dB (SD 50.85). Women had greater average hearing loss than men, and patients treated for head and neck malignancy experienced the greatest cHL.Conclusions Aspirin did not protect from cisplatin-related ototoxicity. Cisplatin and gentamicin may therefore have distinct ototoxic mechanisms, or cisplatin-induced ototoxicity may be refractory to the aspirin regimen used here..
Pender, A.
Rana, S.
Delgado, E.I.
Proszek, P.
Garcia-Murillas, I.
Bhosle, J.
O'Brien, M.
Palma, J.F.
Turner, N.C.
Popat, S.
Downward, J.
Gonzalez, D.
(2016). 3 EGFR mutant circulating tumour DNA detection in advanced lung adenocarcinoma: optimising the application of a ctDNA diagnostic to real world clinical practice. Lung cancer,
Vol.91,
pp. S2-S2.
Puglisi, M.
Stewart, A.
Thavasu, P.
Frow, M.
Carreira, S.
Minchom, A.
Punwani, R.
Bhosle, J.
Popat, S.
Ratoff, J.
de Bono, J.
Yap, T.A.
O''Brien, M.
Banerji, U.
(2016). Characterisation of the Phosphatidylinositol 3-Kinase Pathway in Non-Small Cell Lung Cancer Cells Isolated from Pleural Effusions. Oncology,
Vol.90
(5),
pp. 280-288.
show abstract
Objectives We hypothesised that it was possible to quantify phosphorylation of important nodes in the phosphatidylinositol 3-kinase (PI3K) pathway in cancer cells isolated from pleural effusions of patients with non-small cell lung cancer (NSCLC) and study their correlation to somatic mutations and clinical outcomes.Materials and methods Cells were immunomagnetically separated from samples of pleural effusion in patients with NSCLC. p-AKT, p-S6K and p-GSK3β levels were quantified by ELISA; targeted next-generation sequencing was used to characterise mutations in 26 genes.Results It was possible to quantify phosphoproteins in cells isolated from 38/43 pleural effusions. There was a significant correlation between p-AKT and p-S6K levels [r = 0.85 (95% confidence interval 0.73-0.92), p < 0.0001], but not p-AKT and p-GSK3β levels [r = 0.19 (95% confidence interval -0.16 to 0.5), p = 0.3]. A wide range of mutations was described and p-S6K was higher in samples that harboured at least one mutation compared to those that did not (p = 0.03). On multivariate analysis, p-S6K levels were significantly associated with poor survival (p < 0.01).Conclusion Our study has shown a correlation between p-AKT levels and p-S6K, but not GSK3β, suggesting differences in regulation of the distal PI3K pathway by AKT. Higher p-S6K levels were associated with adverse survival, making it a critically important target in NSCLC..
Kumar, R.
Lu, S.K.
Minchom, A.
Sharp, A.
Davidson, M.
Gunapala, R.
Yap, T.A.
Bhosle, J.
Popat, S.
O’Brien, M.E.
(2016). A phase 1b trial of the combination of an all-oral regimen of capecitabine and erlotinib in advanced non-small cell lung cancer in Caucasian patients. Cancer chemotherapy and pharmacology,
Vol.77
(2),
pp. 375-383.
Marquez-Medina, D.
Martin-Marco, A.
Popat, S.
(2016). Watch the weathercock: changes in re-staging 18F-FDG PET/CT scan predict the probability of relapse in locally advanced non-small cell lung cancer. Clinical and translational oncology,
Vol.18
(2),
pp. 228-232.
Abdelraouf, F.
Smit, E.
Hasan, B.
Menis, J.
Popat, S.
van Meerbeeck, J.P.
Surmont, V.F.
Baas, P.
O'Brien, M.
(2016). Sunitinib (SU11248) in patients with chemo naive extensive small cell lung cancer or who have a ‘chemosensitive’ relapse: A single-arm phase II study (EORTC-08061). European journal of cancer,
Vol.54,
pp. 35-39.
Malottki, K.
Popat, S.
Deeks, J.J.
Riley, R.D.
Nicholson, A.G.
Billingham, L.
(2016). Problems of variable biomarker evaluation in stratified medicine research—A case study of ERCC1 in non-small-cell lung cancer. Lung cancer,
Vol.92,
pp. 1-7.
Marquez-Medina, D.
Popat, S.
(2016). Eventual role of EGFR-tyrosine kinase inhibitors in early-stage non-small-cell lung cancer. Future oncology,
Vol.12
(6),
pp. 815-825.
show abstract
Nonadvanced non-small-cell lung cancer (NSCLC) has a poor long-term survival from surgery or definitive radiation that is minimally improved with induction/adjuvant conventional chemotherapy. EGFR-tyrosine kinase inhibitors (TKIs), which provide a significant benefit for molecularly selected EGFR-mutant patients with advanced NSCLC, have been infrequently explored in nonadvanced NSCLC to date. Current published studies reported no significant benefit from adding EGFR-TKI to the induction/adjuvant setting. However, many of them present eventual biases such as unpowered statistics, lack of molecular selection, recruitment of low-risk NSCLC, low sample size or unsuitable control arms. Results, strengths and deficiencies of completed and ongoing trials were fully discussed. Similarly, the selection of patients and control arms, the duration and risks of EGFR-TKI therapies in early-stage NSCLC, the evaluation of response and the diagnosis of EGFR status were considered and analyzed. .
Schuler, M.
Wu, Y.-.
Hirsh, V.
O’Byrne, K.
Yamamoto, N.
Mok, T.
Popat, S.
Sequist, L.V.
Massey, D.
Zazulina, V.
Yang, J.C.
(2016). First-Line Afatinib versus Chemotherapy in Patients with Non–Small Cell Lung Cancer and Common Epidermal Growth Factor Receptor Gene Mutations and Brain Metastases. Journal of thoracic oncology,
Vol.11
(3),
pp. 380-390.
Schuler, M.
Yang, J.C.
Park, K.
Kim, J.-.
Bennouna, J.
Chen, Y.-.
Chouaid, C.
De Marinis, F.
Feng, J.-.
Grossi, F.
Kim, D.-.
Liu, X.
Lu, S.
Strausz, J.
Vinnyk, Y.
Wiewrodt, R.
Zhou, C.
Wang, B.
Chand, V.K.
Planchard, D.
Ignatius Ou, S.
Planchard, D.
Park, K.
Schuler, M.
Yang, J.
Chand, V.
Rohr, K.
Bagnes, C.
Martin, C.M.
Recondo, G.
Zarba, J.J.
Blajman, C.
Richardet, M.
McLachlan, S.-.
Parente, P.
Underhill, C.
Crombie, C.
Mainwaring, P.
Greil, R.
Humblet, Y.
Bustin, F.
Carestia, L.
Galdermans, D.
Lambrechts, M.
Delval, L.
Vercauter, P.
Zhou, C.
Wang, J.
Huang, C.
Lin, X.
Wu, Y.
Liu, X.
Cheng, Y.
Qin, S.
Feng, J.
Huang, J.
Zhang, Y.
Lu, S.
Zereu, M.
Garicochea, B.
Zadra, C.A.
Riska, H.
Alanko, T.
Cadranel, J.
Chouaid, C.
Zalcman, G.
Sibilot, D.M.
Perol, M.
Planchard, D.
Bennouna, J.
Fournel, P.
Gervais, R.
Rotarski, M.
Coudert, B.
Schuler, M.
Thomas, M.
Wehler, T.
Faehling, M.
Keilholz, U.
Laack, E.
von Pawel, J.
Huber, R.
Dickgreber, N.
Wiewrodt, R.
Mark, Z.
Tehenes, S.
Strausz, J.
Sarosi, V.
Prabhash, K.
Jain, M.
Venkatesan, S.
Sharma, L.
Dadhich, H.
Nagarkar, R.V.
Onn, A.
Gottfried, M.
Stemmer, S.
Migliorino, M.R.
Grossi, F.
Bidoli, P.
Bearz, A.
Gridelli, C.
Milandri, C.
Platania, M.
Ceresoli, G.L.
Cruciani, G.
Delgado, F.G.
Gonzalez Perez, J.L.
Luna, G.A.
Baca, O.P.
Aerts, J.G.
Stigt, J.A.
Dingemans, A.M.
Herder, G.J.
Gans, S.J.
Salas Sánchez, J.F.
Alvarez Barreda, R.L.
Pantigoso, W.R.
Palomino, O.L.
Jaskiewicz, P.
Kazarnowicz, A.
Serwatowski, P.
Szczesna, A.
Jassem, J.
Lubennikov, V.
Karaseva, N.
Orlov, S.
Ragulin, Y.
Garrido, P.
González Larriba, J.L.
Camps, C.
Campelo, R.G.
Lianes, P.
Cobo, M.
Felip, E.
Kim, D.-.
Kim, S.-.
Park, K.
Kim, J.-.
Han, J.-.
Kim, Y.-.
Yang, C.-.
Hsia, T.-.
Chen, Y.-.
Tsai, Y.-.
Chang, G.-.
Tsao, T.C.
Su, W.-.
Huang, M.-.
Ho, C.-.
Hsieh, R.-.
Vinnyk, Y.
Popovych, O.
Ponomarova, O.
Bondarenko, I.
Polishchuk, I.
Shah, R.
Mitra, S.
Popat, S.
Spicer, J.
Toy, E.
Popat, S.
Talbot, T.
Brown, E.
Upadhyay, S.
Summers, Y.
Gurtler, J.
Meza, L.
Thropay, J.
(2016). Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial. Annals of oncology,
Vol.27
(3),
pp. 417-423.
Anandappa, G.
Popat, S.
(2016). Management of lung cancer. Medicine,
Vol.44
(4),
pp. 244-248.
Weller, A.
O'Brien, M.E.
Ahmed, M.
Popat, S.
Bhosle, J.
McDonald, F.
Yap, T.A.
Du, Y.
Vlahos, I.
deSouza, N.M.
(2016). Mechanism and non-mechanism based imaging biomarkers for assessing biological response to treatment in non-small cell lung cancer. European journal of cancer (oxford, england : 1990),
Vol.59,
pp. 65-78.
show abstract
Therapeutic options in locally advanced non-small cell lung cancer (NSCLC) have expanded in the past decade to include a palate of targeted interventions such as high dose targeted thermal ablations, radiotherapy and growing platform of antibody and small molecule therapies and immunotherapies. Although these therapies have varied mechanisms of action, they often induce changes in tumour architecture and microenvironment such that response is not always accompanied by early reduction in tumour mass, and evaluation by criteria other than size is needed to report more effectively on response. Functional imaging techniques, which probe the tumour and its microenvironment through novel positron emission tomography and magnetic resonance imaging techniques, offer more detailed insights into and quantitation of tumour response than is available on anatomical imaging alone. Use of these biomarkers, or other rational combinations as readouts of pathological response in NSCLC have potential to provide more accurate predictors of treatment outcomes. In this article, the robustness of the more commonly available positron emission tomography and magnetic resonance imaging biomarker indices is examined and the evidence for their application in NSCLC is reviewed..
Sharp, A.
Bhosle, J.
Abdelraouf, F.
Popat, S.
O'Brien, M.
Yap, T.A.
(2016). Development of molecularly targeted agents and immunotherapies in small cell lung cancer. European journal of cancer (oxford, england : 1990),
Vol.60,
pp. 26-39.
show abstract
Small cell lung cancer (SCLC) is a smoking-induced malignancy with multiple toxin-associated mutations, which accounts for 15% of all lung cancers. It remains a clinical challenge with a rapid doubling time, early dissemination and poor prognosis. Despite multiple clinical trials in SCLC, platinum-based chemotherapy remains the mainstay of treatment in the first line advanced disease setting; good initial responses are nevertheless inevitably followed by disease relapse and survival ultimately remains poor. There are currently no molecularly targeted agents licenced for use in SCLC. Advances in sequencing the cancer genome and other high-throughput profiling technologies have identified aberrant pathways and mechanisms implicated in SCLC development and progression. Novel anti-tumour therapeutics that impact these putative targets are now being developed and investigated in SCLC. In this review, we discuss novel anti-tumour agents assessed in SCLC with reference to the complex molecular mechanisms implicated in SCLC development and progression. We focus on novel DNA damage response inhibitors, immune checkpoint modulators and antibody-drug conjugates that have shown promise in SCLC, and which may potentially transform treatment strategies in this disease. Finally, we envision the future management of SCLC and propose a biomarker-driven translational treatment paradigm for SCLC that incorporates next generation sequencing studies with patient tumours, circulating plasma DNA and functional imaging. Such modern strategies have the potential to transform the management and improve patient outcomes in SCLC..
Minchom, A.
Punwani, R.
Filshie, J.
Bhosle, J.
Nimako, K.
Myerson, J.
Gunapala, R.
Popat, S.
O'Brien, M.E.
(2016). A randomised study comparing the effectiveness of acupuncture or morphine versus the combination for the relief of dyspnoea in patients with advanced non-small cell lung cancer and mesothelioma. European journal of cancer,
Vol.61,
pp. 102-110.
Viola, P.
Maurya, M.
Croud, J.
Gazdova, J.
Suleman, N.
Lim, E.
Newsom-Davis, T.
Plowman, N.
Rice, A.
Montero, M.A.
Gonzalez de Castro, D.
Popat, S.
Nicholson, A.G.
(2016). A Validation Study for the Use of ROS1 Immunohistochemical Staining in Screening for ROS1 Translocations in Lung Cancer. Journal of thoracic oncology,
Vol.11
(7),
pp. 1029-1039.
Pearson, A.
Smyth, E.
Babina, I.S.
Herrera-Abreu, M.T.
Tarazona, N.
Peckitt, C.
Kilgour, E.
Smith, N.R.
Geh, C.
Rooney, C.
Cutts, R.
Campbell, J.
Ning, J.
Fenwick, K.
Swain, A.
Brown, G.
Chua, S.
Thomas, A.
Johnston, S.R.
Ajaz, M.
Sumpter, K.
Gillbanks, A.
Watkins, D.
Chau, I.
Popat, S.
Cunningham, D.
Turner, N.C.
(2016). High-Level Clonal FGFR Amplification and Response to FGFR Inhibition in a Translational Clinical Trial. Cancer discovery,
Vol.6
(8),
pp. 838-851.
show abstract
Unlabelled FGFR1 and FGFR2 are amplified in many tumor types, yet what determines response to FGFR inhibition in amplified cancers is unknown. In a translational clinical trial, we show that gastric cancers with high-level clonal FGFR2 amplification have a high response rate to the selective FGFR inhibitor AZD4547, whereas cancers with subclonal or low-level amplification did not respond. Using cell lines and patient-derived xenograft models, we show that high-level FGFR2 amplification initiates a distinct oncogene addiction phenotype, characterized by FGFR2-mediated transactivation of alternative receptor kinases, bringing PI3K/mTOR signaling under FGFR control. Signaling in low-level FGFR1-amplified cancers is more restricted to MAPK signaling, limiting sensitivity to FGFR inhibition. Finally, we show that circulating tumor DNA screening can identify high-level clonally amplified cancers. Our data provide a mechanistic understanding of the distinct pattern of oncogene addiction seen in highly amplified cancers and demonstrate the importance of clonality in predicting response to targeted therapy.Significance Robust single-agent response to FGFR inhibition is seen only in high-level FGFR-amplified cancers, with copy-number level dictating response to FGFR inhibition in vitro, in vivo, and in the clinic. High-level amplification of FGFR2 is relatively rare in gastric and breast cancers, and we show that screening for amplification in circulating tumor DNA may present a viable strategy to screen patients. Cancer Discov; 6(8); 838-51. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 803..
Marquez-Medina, D.
Popat, S.
(2016). Closing faucets: the role of anti-angiogenic therapies in malignant pleural diseases. Clinical and translational oncology,
Vol.18
(8),
pp. 760-768.
Novello, S.
Barlesi, F.
Califano, R.
Cufer, T.
Ekman, S.
Levra, M.G.
Kerr, K.
Popat, S.
Reck, M.
Senan, S.
Simo, G.V.
Vansteenkiste, J.
Peters, S.
(2016). Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of oncology,
Vol.27,
pp. v1-v27.
Khalifa, J.
Amini, A.
Popat, S.
Gaspar, L.E.
Faivre-Finn, C.
(2016). Brain Metastases from NSCLC: Radiation Therapy in the Era of Targeted Therapies. Journal of thoracic oncology,
Vol.11
(10),
pp. 1627-1643.
Pender, A.
Garcia-Murillas, I.
Rana, S.
Cutts, R.J.
Kelly, G.
Fenwick, K.
Kozarewa, I.
Gonzalez de Castro, D.
Bhosle, J.
O'Brien, M.
Turner, N.C.
Popat, S.
Downward, J.
(2015). Efficient Genotyping of KRAS Mutant Non-Small Cell Lung Cancer Using a Multiplexed Droplet Digital PCR Approach. Plos one,
Vol.10
(9),
pp. e0139074-?.
show abstract
Droplet digital PCR (ddPCR) can be used to detect low frequency mutations in oncogene-driven lung cancer. The range of KRAS point mutations observed in NSCLC necessitates a multiplex approach to efficient mutation detection in circulating DNA. Here we report the design and optimisation of three discriminatory ddPCR multiplex assays investigating nine different KRAS mutations using PrimePCR™ ddPCR™ Mutation Assays and the Bio-Rad QX100 system. Together these mutations account for 95% of the nucleotide changes found in KRAS in human cancer. Multiplex reactions were optimised on genomic DNA extracted from KRAS mutant cell lines and tested on DNA extracted from fixed tumour tissue from a cohort of lung cancer patients without prior knowledge of the specific KRAS genotype. The multiplex ddPCR assays had a limit of detection of better than 1 mutant KRAS molecule in 2,000 wild-type KRAS molecules, which compared favourably with a limit of detection of 1 in 50 for next generation sequencing and 1 in 10 for Sanger sequencing. Multiplex ddPCR assays thus provide a highly efficient methodology to identify KRAS mutations in lung adenocarcinoma..
Aitken, K.
Popat, S.
Nutting, C.
McDonald, F.
(2015). 76: Patterns of extra-cranial disease progression in epidermal growth factor receptor (EGFR) mutant metastatic non-small cell lung cancer (NSCLC) patients on a tyrosine kinase inhibitor (TKI). Lung cancer,
Vol.87,
pp. S30-S30.
Popat, S.
Mellemgaard, A.
Fahrbach, K.
Martin, A.
Rizzo, M.
Kaiser, R.
Griebsch, I.
Reck, M.
(2015). Nintedanib plus docetaxel as second-line therapy in patients with non-small-cell lung cancer: a network meta-analysis. Future oncology,
Vol.11
(3),
pp. 409-420.
show abstract
ABSTRACT Background: Nintedanib plus docetaxel has proven an overall survival benefit over docetaxel monotherapy in second-line treatment of non-small-cell lung cancer of adenocarcinoma histology in the LUME-Lung 1 pivotal trial. No published trials have previously compared nintedanib plus docetaxel with agents – other than docetaxel – that are approved second-line treatments for non-small-cell lung cancer. Methods: The relative efficacy of nintedanib plus docetaxel versus second-line agents was evaluated by conducting a network meta-analysis of progression-free survival and overall survival. Results: Nine suitable studies were identified. The estimated probability of nintedanib plus docetaxel being the best treatment with regard to overall survival was 70% (versus 16% for pemetrexed, 10% for docetaxel and 3% for erlotinib). Results for progression-free survival were similar. Conclusion: In patients with advanced non-small-cell lung cancer of adenocarcinoma histology, results suggest that nintedanib plus docetaxel offers clinical benefit compared with docetaxel alone, when used as second-line treatment, and suggests that this combination may also add clinical benefit compared with erlotinib in this patient group. .
Yang, J.C.
Wu, Y.-.
Schuler, M.
Sebastian, M.
Popat, S.
Yamamoto, N.
Zhou, C.
Hu, C.-.
O'Byrne, K.
Feng, J.
Lu, S.
Huang, Y.
Geater, S.L.
Lee, K.Y.
Tsai, C.-.
Gorbunova, V.
Hirsh, V.
Bennouna, J.
Orlov, S.
Mok, T.
Boyer, M.
Su, W.-.
Lee, K.H.
Kato, T.
Massey, D.
Shahidi, M.
Zazulina, V.
Sequist, L.V.
(2015). Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. The lancet oncology,
Vol.16
(2),
pp. 141-151.
Scagliotti, G.V.
Bondarenko, I.
Blackhall, F.
Barlesi, F.
Hsia, T.-.
Jassem, J.
Milanowski, J.
Popat, S.
Sanchez-Torres, J.M.
Novello, S.
Benner, R.J.
Green, S.
Molpus, K.
Soria, J.-.
Shepherd, F.A.
(2015). Randomized, phase III trial of figitumumab in combination with erlotinib versus erlotinib alone in patients with nonadenocarcinoma nonsmall-cell lung cancer. Annals of oncology,
Vol.26
(3),
pp. 497-504.
Lim, E.
Nicholson, A.G.
Padley, S.
Popat, S.
(2015). Never smoker with ground glass opacities on CT. The lancet respiratory medicine,
Vol.3
(4),
pp. 328-328.
Pender, A.
Popat, S.
(2015). The efficacy of crizotinib in patients with ALK-positive nonsmall cell lung cancer. Therapeutic advances in respiratory disease,
Vol.9
(3),
pp. 97-104.
show abstract
Molecular profiling of nonsmall cell lung cancer (NSCLC) contributes to better understanding the different molecular subtypes of this heterogeneous group of diseases. The discovery of oncogenic ALK rearrangements in NSCLC and the subsequent success in their therapeutic targeting with crizotinib reinforces the benefits of a precision approach to systemic anticancer therapy. In addition, the rapid development of crizotinib from first discovery thorough accelerated US Food and Drug Administration approval, and late stage confirmatory clinical trials, exemplifies the success of the drug development strategy of close collaboration between clinicians, industry and regulatory authorities. In this review we describe the identification of ALK rearranged NSCLC, clinical characteristics of such patients, and clinical outcomes when treated with crizotinib. .
Hall, P.E.
Spicer, J.
Popat, S.
(2015). Rationale for targeting the ErbB family of receptors in patients with advanced squamous cell carcinoma of the lung. Future oncology,
Vol.11
(15),
pp. 2175-2191.
show abstract
Squamous cell carcinoma (SCC) of the lung represents around 30% of all non-small-cell lung cancers. Treatment options for nonsquamous histology have increased in recent years following the development of pemetrexed chemotherapy and the identification of activating EGFR mutations and ALK rearrangements as targets for effective noncytotoxic agents. By contrast, until recently the development of new therapies for SCC has lagged behind. However, the identification of important genetic events driving SCC, including a greater understanding of the role of the ErbB receptor family in SCC pathogenesis, as well as recent immunotherapy advances, have led to new treatment options for SCC. .
O’Brien, M.E.
Gaafar, R.
Hasan, B.
Menis, J.
Cufer, T.
Popat, S.
Woll, P.J.
Surmont, V.
Georgoulias, V.
Montes, A.
Blackhall, F.
Hennig, I.
Schmid-Bindert, G.
Baas, P.
(2015). Maintenance pazopanib versus placebo in Non-Small Cell Lung Cancer patients non-progressive after first line chemotherapy: A double blind randomised phase III study of the lung cancer group, EORTC 08092 (EudraCT: 2010-018566-23, NCT01208064). European journal of cancer,
Vol.51
(12),
pp. 1511-1528.
Soria, J.-.
Felip, E.
Cobo, M.
Lu, S.
Syrigos, K.
Lee, K.H.
Göker, E.
Georgoulias, V.
Li, W.
Isla, D.
Guclu, S.Z.
Morabito, A.
Min, Y.J.
Ardizzoni, A.
Gadgeel, S.M.
Wang, B.
Chand, V.K.
Goss, G.D.
(2015). Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. The lancet oncology,
Vol.16
(8),
pp. 897-907.
Stephens, R.J.
Whiting, C.
Cowan, K.
(2015). Research priorities in mesothelioma: A James Lind Alliance Priority Setting Partnership. Lung cancer,
Vol.89
(2),
pp. 175-180.
Middleton, G.
Popat, S.
Walker, I.
Mulatero, C.
Spicer, J.
Summers, Y.
Yap, T.A.
Crack, L.R.
Billingham, L.J.
(2015). The National Lung Matrix Trial: Multi-Drug, Genetic Marker-Directed, Multi-Arm Phase II Trial in Non-Small Cell Lung Cancer. Journal of thoracic oncology,
Vol.10
(9),
pp. S763-S764.
Billingham, L.J.
Brock, K.
Crack, L.R.
Popat, S.
Middleton, G.
(2015). Using a Bayesian Adaptive Phase II Trial Design to Test Multiple Genetic-Marker-Directed Drugs in the National Lung Matrix Trial. Journal of thoracic oncology,
Vol.10
(9),
pp. S372-S372.
Marquez-Medina, D.
Popat, S.
(2015). Afatinib: a second-generation EGF receptor and ErbB tyrosine kinase inhibitor for the treatment of advanced non-small-cell lung cancer. Future oncology,
Vol.11
(18),
pp. 2525-2540.
show abstract
First-generation reversible EGF receptor (EGFR) tyrosine kinase inhibitors (TKIs) changed our understanding of advanced non-small-cell lung cancer biology and behavior. The presence of sensitizing EGFR mutations in advanced non-small-cell lung cancer defines a subset of patients with a better prognosis and sensitivity to EGFR-TKIs with a better response rate, progression-free survival, quality of life and symptom control than with chemotherapy in the first-line therapy setting. However, current EGFR-TKIs show minimal responses in EGFR wild-type patients or with acquired TKI resistance mediated through the EGFR T790M allele. Afatinib is an irreversible pan-ErbB-TKI, active against wild-type EGFR, sensitizing and T970M-mutant EGFR, ErbB2 and ErbB4 receptors, and represents a step change between reversible first-generation and future irreversible highly specific third-generation EGFR-TKIs. Here, we review the clinical development of afatinib through the LUX-Lung trials portfolio highlighting benefits and toxicities. .
Gennatas, S.
Anbunathan, H.
Montero, A.
Nicholson, A.G.
Popat, S.
Bowcock, A.M.
(2015). Validation of a Specific Missense GTF2I Mutation in More Indolent Thymic Epithelial Tumours. Journal of thoracic oncology,
Vol.10
(9),
pp. S403-S403.
Marquez-Medina, D.
Popat, S.
(2015). Systemic therapy for pulmonary carcinoids. Lung cancer,
Vol.90
(2),
pp. 139-147.
Cheng, L.
Tunariu, N.
Collins, D.J.
Blackledge, M.D.
Riddell, A.M.
Leach, M.O.
Popat, S.
Koh, D.-.
(2015). Response evaluation in mesothelioma: Beyond RECIST. Lung cancer,
Vol.90
(3),
pp. 433-441.
Abdelraouf, F.
Sharp, A.
Maurya, M.
Mair, D.
Wotherspoon, A.
Leary, A.
Gonzalez de Castro, D.
Bhosle, J.
Nassef, A.
Gaafar, T.
Popat, S.
Yap, T.A.
O’Brien, M.
(2015). Focused molecular analysis of small cell lung cancer: feasibility in routine clinical practice. Bmc research notes,
Vol.8
(1).
Balachandran, K.
Okines, A.
Gunapala, R.
Morganstein, D.
Popat, S.
(2015). Resolution of severe hyponatraemia is associated with improved survival in patients with cancer. Bmc cancer,
Vol.15
(1).
Middleton, G.
Crack, L.R.
Popat, S.
Swanton, C.
Hollingsworth, S.J.
Buller, R.
Walker, I.
Carr, T.H.
Wherton, D.
Billingham, L.J.
(2015). The National Lung Matrix Trial: translating the biology of stratification in advanced non-small-cell lung cancer. Annals of oncology : official journal of the european society for medical oncology,
Vol.26
(12),
pp. 2464-2469.
show abstract
Background The management of NSCLC has been transformed by stratified medicine. The National Lung Matrix Trial (NLMT) is a UK-wide study exploring the activity of rationally selected biomarker/targeted therapy combinations.Patients and methods The Cancer Research UK (CRUK) Stratified Medicine Programme 2 is undertaking the large volume national molecular pre-screening which integrates with the NLMT. At study initiation, there are eight drugs being used to target 18 molecular cohorts. The aim is to determine whether there is sufficient signal of activity in any drug-biomarker combination to warrant further investigation. A Bayesian adaptive design that gives a more realistic approach to decision making and flexibility to make conclusions without fixing the sample size was chosen. The screening platform is an adaptable 28-gene Nextera next-generation sequencing platform designed by Illumina, covering the range of molecular abnormalities being targeted. The adaptive design allows new biomarker-drug combination cohorts to be incorporated by substantial amendment. The pre-clinical justification for each biomarker-drug combination has been rigorously assessed creating molecular exclusion rules and a trumping strategy in patients harbouring concomitant actionable genetic abnormalities. Discrete routes of pathway activation or inactivation determined by cancer genome aberrations are treated as separate cohorts. Key translational analyses include the deep genomic analysis of pre- and post-treatment biopsies, the establishment of patient-derived xenograft models and longitudinal ctDNA collection, in order to define predictive biomarkers, mechanisms of resistance and early markers of response and relapse.Conclusion The SMP2 platform will provide large scale genetic screening to inform entry into the NLMT, a trial explicitly aimed at discovering novel actionable cohorts in NSCLC.Clinical trial isrctn 38344105..
Gennatas, S.
Noble, J.
Stanway, S.
Gunapala, R.
Chowdhury, R.
Wotherspoon, A.
Benepal, T.
Popat, S.
(2015). Patterns of relapse in extrapulmonary small cell carcinoma: retrospective analysis of outcomes from two cancer centres. Bmj open,
Vol.5
(1),
pp. e006440-e006440.
Marquez-Medina, D.
Popat, S.
(2015). Steroid-related emphysematous cystitis in an EGFR-mutant patient with lung adenocarcinoma while on gefitinib treatment. Cancer treatment communications,
Vol.4,
pp. 86-88.
Pender, A.
Coward, J.
Gunapala, R.
Bhosle, J.
O'Brien, M.
Popat, S.
(2014). 38 Patterns of relapse and detection method in patients with resected non-small cell lung cancer (NSCLC) – a single institution experience. Lung cancer,
Vol.83,
pp. S15-S15.
Freidin, M.B.
Mair, D.
Tay, A.
Freydina, D.V.
Chudasama, D.
Popat, S.
Nicholson, A.G.
Rice, A.
Montero-Fernandez, A.
Anikin, V.
de Castro, D.G.
Lim, E.
(2014). 8 The utility of peripheral blood circulating tumour cells for the detection of KRAS, EGFR and BRAF mutations in primary lung cancer. Lung cancer,
Vol.83,
pp. S3-S4.
Popat, S.
(2014). Patient reported outcomes from LUX-Lung 3: first-line afatinib is superior to chemotherapy-would patients agree?. Annals of palliative medicine,
Vol.3
(1),
pp. 19-21.
show abstract
The LUX-Lung 3 trial was an important randomized phase 3 trial in patients with EGFR mutant advanced non-small cell lung cancer (NSCLC). Here, patients were randomized to either afatinib or cisplatin-pemetrexed and the primary endpoint of progression-free survival (PFS) was easily met (HR=0.58, P=0.001). This was the first large-scale trial of this type using a modern chemotherapy comparator, including Asian and non-Asian patients, central radiology review, and utilizing comprehensive patient-reported outcomes. Whilst efficacy for afatinib was markedly superior to chemotherapy, do the patient-reported outcomes reflect this superiority? The symptom control and quality of life (QoL) data from this trial has now been published. Analysis of these demonstrate clear superiority of afatinib over chemotherapy for delay in cough deterioration, and dyspnoea. Notably, given the toxicity profile of afatinib, these improvements translated into significant improvements in global health status, physical, role, and cognitive functioning. The clinical benefits for afatinib over cisplatin-pemetrexed chemotherapy for EGFR mutation-positive advanced non-small cell lung patients seem overwhelming, and are clinically meaningful. These results are also consistent with QoL data from other trials of gefitinib/erlotinib, but much more robust, given the larger patient numbers. Would patients agree that afatinib is superior to chemotherapy? On the basis of data presented, the answer is probably "Yes". However, the key unanswered question remaining is "Which is the best EGFR-tyrosine kinase inhibitor (TKI) to use up front?" and we will have to wait until ongoing trial data can help answer this..
Twelves, C.
Chmielowska, E.
Havel, L.
Popat, S.
Swieboda-Sadlej, A.
Sawrycki, P.
Bycott, P.
Ingrosso, A.
Kim, S.
Williams, J.A.
Chen, C.
Olszanski, A.J.
de Besi, P.
Schiller, J.H.
(2014). Randomised phase II study of axitinib or bevacizumab combined with paclitaxel/carboplatin as first-line therapy for patients with advanced non-small-cell lung cancer. Annals of oncology,
Vol.25
(1),
pp. 132-138.
Abdelraouf, F.
de Castro, D.G.
Wotherspoon, A.
Maurya, M.
Mair, D.
Bhosle, J.
Popat, S.
O'Brien, M.
(2014). INVESTIGATING MOLECULAR BIOMARKERS IN SCLC. Journal of thoracic oncology,
Vol.9
(4),
pp. S30-S30.
McDonald, F.
Popat, S.
(2014). Combining targeted agents and hypo- and hyper-fractionated radiotherapy in NSCLC. Journal of thoracic disease,
Vol.6
(4),
pp. 356-368.
Le Quesne, J.
Maurya, M.
Yancheva, S.G.
O’Brien, M.
Popat, S.
Wotherspoon, A.C.
de Castro, D.G.
Nicholson, A.G.
(2014). A Comparison of Immunohistochemical Assays and FISH in Detecting the ALK Translocation in Diagnostic Histological and Cytological Lung Tumor Material. Journal of thoracic oncology,
Vol.9
(6),
pp. 769-774.
Pender, A.
Popat, S.
(2014). Understanding lung cancer molecular subtypes. Clinical practice,
Vol.11
(4),
pp. 441-453.
Patton, S.
Normanno, N.
Blackhall, F.
Murray, S.
Kerr, K.M.
Dietel, M.
Filipits, M.
Benlloch, S.
Popat, S.
Stahel, R.
Thunnissen, E.
(2014). Assessing standardization of molecular testing for non-small-cell lung cancer: results of a worldwide external quality assessment (EQA) scheme for EGFR mutation testing. British journal of cancer,
Vol.111
(2),
pp. 413-420.
Khan, F.
Ottensmeier, C.
Popat, S.
Dua, D.
Dorey, N.
Ellis, S.
Szabo, M.
Upadhyay, S.
Califano, R.
Chan, S.
Lee, L.
Ali, C.W.
Nicolson, M.
Bates, A.T.
Button, M.
Chaudhuri, A.
Mulvenna, P.
Shaw, H.M.
Danson, S.J.
(2014). Afatinib use in non-small cell lung cancer previously sensitive to epidermal growth factor receptor inhibitors: The United Kingdom Named Patient Programme. European journal of cancer,
Vol.50
(10),
pp. 1717-1721.
Puglisi, M.
Thavasu, P.
Stewart, A.
de Bono, J.S.
O’Brien, M.E.
Popat, S.
Bhosle, J.
Banerji, U.
(2014). AKT inhibition synergistically enhances growth-inhibitory effects of gefitinib and increases apoptosis in non-small cell lung cancer cell lines. Lung cancer,
Vol.85
(2),
pp. 141-146.
Popat, S.
Mok, T.
Yang, J.C.
Wu, Y.-.
Lungershausen, J.
Stammberger, U.
Griebsch, I.
Fonseca, T.
Paz-Ares, L.
(2014). Afatinib in the treatment of EGFR mutation-positive NSCLC – A network meta-analysis. Lung cancer,
Vol.85
(2),
pp. 230-238.
O'Brien, M.E.
Gaafar, R.
Hasan, B.
Menis, J.
Cufer, T.
Popat, S.
Woll, P.
Surmont, V.
Georgoulias, V.
Montes, A.
Blackhall, F.
Hennig, I.
Schmid-Bindert, G.
Baas, P.
(2014). Double Blind Randomized Phase III Study of Maintenance Pazopanib® (Pz) Versus Placebo (P) in Non Small Cell Lung Cancer (Nsclc) Patients (Pts) Non Progressive After First Line Chemotherapy [Ct] (Eortc Lung Cancer Group, 08092): Mapping. Annals of oncology,
Vol.25,
pp. iv435-iv435.
Freydin, M.
Freydina, D.V.
Chudasama, D.
Leung, M.
Popat, S.
Gonzalez-De-Castro, D.
Rice, A.
Fernandez, A.M.
Nicholson, A.G.
Lim, E.
(2014). A Blood Based Egfr Mutation Analysis in Circulating Plasma Dna for Prediction of Primary Tumour Mutations in Lung Cancer. Annals of oncology,
Vol.25,
pp. iv68-iv68.
Reck, M.
Popat, S.
Reinmuth, N.
De Ruysscher, D.
Kerr, K.M.
Peters, S.
(2014). Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of oncology,
Vol.25,
pp. iii27-iii39.
Gann, C.-.
Reck, M.
Leighl, N.
Nowak, A.
Pavlakis, N.
Popat, S.
Sorensen, J.B.
Mueller, M.
Von Wangenheim, U.
Scagliotti, G.
(2014). NINTEDANIB PLUS PEMETREXED/CISPLATIN FOLLOWED BY MAINTENANCE NINTEDANIB FOR UNRESECTABLE MALIGNANT PLEURAL MESOTHELIOMA-AN INTERNATIONAL, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE II STUDY. Journal of thoracic oncology,
Vol.9
(9),
pp. S172-S172.
Rossi, A.
Chiodini, P.
Sun, J.-.
O'Brien, M.E.
von Plessen, C.
Barata, F.
Park, K.
Popat, S.
Bergman, B.
Parente, B.
Gallo, C.
Gridelli, C.
Perrone, F.
Di Maio, M.
(2014). Six versus fewer planned cycles of first-line platinum-based chemotherapy for non-small-cell lung cancer: a systematic review and meta-analysis of individual patient data. The lancet oncology,
Vol.15
(11),
pp. 1254-1262.
Popat, S.
Lungershausen, J.
Griebsch, I.
Marten, A.
Wu, Y.L.
(2014). Treatments for EGFR Mutation-Positive (M+) NSCLC Patients – A Network Meta-Analysis (NMA) by Mutation Type. Value in health,
Vol.17
(7),
pp. A615-A615.
Minchom, A.R.
Saksornchai, K.
Bhosle, J.
Gunapala, R.
Puglisi, M.
Lu, S.K.
Nimako, K.
Coward, J.
Yu, K.C.
Bordi, P.
Popat, S.
O'Brien, M.E.
(2014). An unblinded, randomised phase II study of platinum-based chemotherapy with vitamin B12and folic acid supplementation in the treatment of lung cancer with plasma homocysteine blood levels as a biomarker of severe neutropenic toxicity. Bmj open respiratory research,
Vol.1
(1),
pp. e000061-e000061.
Linch, M.
Gennatas, S.
Kazikin, S.
Iqbal, J.
Gunapala, R.
Priest, K.
Severn, J.
Norton, A.
Ayite, B.
Bhosle, J.
O’Brien, M.
Popat, S.
(2014). A serum mesothelin level is a prognostic indicator for patients with malignant mesothelioma in routine clinical practice. Bmc cancer,
Vol.14
(1).
Pender, A.
Coward, J.
Gunapala, R.
Bhosle, J.
O'Brien, M.
Popat, S.
(2013). 33 Outcomes of patients undergoing adjuvant platinum–vinorelbine chemotherapy for resected non-small cell lung cancer (NSCLC). Lung cancer,
Vol.79,
pp. S12-S12.
NIMAKO, K.
GUNAPALA, R.
POPAT, S.
O'BRIEN, M.E.
(2013). Patient factors, health care factors and survival from lung cancer according to ethnic group in the south of London, UK. European journal of cancer care,
Vol.22
(1),
pp. 79-87.
Khan, F.
Ottensmeier, C.
Popat, S.
Danson, S.J.
(2013). 30 Afatanib use in non-small cell cancer patients whose tumours have been previously sensitive to EGFR inhibitors: the UK Named Patient Use experience. Lung cancer,
Vol.79,
pp. S10-S11.
Freidin, M.B.
Tay, A.
Chudasama, D.
Nicholson, A.G.
Rice, A.
Bamsey, O.
Higgins, A.
Popat, S.
Anikin, V.
Lim, E.
(2013). 15 Non-invasive KRAS and EGFR mutation testing of primary lung cancer via peripheral blood circulating tumour cells. Lung cancer,
Vol.79,
pp. S5-S6.
Weickhardt, A.J.
Doebele, R.C.
Purcell, W.T.
Bunn, P.A.
Oton, A.B.
Rothman, M.S.
Wierman, M.E.
Mok, T.
Popat, S.
Bauman, J.
Nieva, J.
Novello, S.
Ou, S.-.
Camidge, D.R.
(2013). Symptomatic reduction in free testosterone levels secondary to crizotinib use in male cancer patients. Cancer,
Vol.119
(13),
pp. 2383-2390.
Popat, S.
Wotherspoon, A.
Nutting, C.M.
Gonzalez, D.
Nicholson, A.G.
O’Brien, M.
(2013). Transformation to “high grade” neuroendocrine carcinoma as an acquired drug resistance mechanism in EGFR-mutant lung adenocarcinoma. Lung cancer,
Vol.80
(1),
pp. 1-4.
Nimako, K.
Lu, S.-.
Ayite, B.
Priest, K.
Winkley, A.
Gunapala, R.
Popat, S.
O'Brien, M.E.
(2013). A Pilot Study of a Novel Home Telemonitoring System for Oncology Patients Receiving Chemotherapy. Journal of telemedicine and telecare,
Vol.19
(3),
pp. 148-152.
show abstract
We examined the accuracy and acceptability of a home telemonitoring system for patients receiving chemotherapy. Patients undergoing two cycles of chemotherapy (over six weeks) used the telemonitoring system to analyse their own blood (capillary) and to enter symptom and temperature data. The blood results obtained from self-testing were compared with those from a venous blood sample analysed in the hospital laboratory analyser (the gold standard). We also documented the number and type of alerts generated by the telemonitoring system. Acceptability (ease of use and patient satisfaction) was assessed using questionnaires. Ten patients (mean age 61 years, 60% female) provided 48-paired samples. None of the patients succeeded in obtaining all blood results within pre-defined limits of agreement (i.e. within 15% for haemoglobin, haematocrit, white cell count; and 20% for neutrophil count) during the study. However, the level of clinical agreement between the system and the laboratory standard was good; only three out of the 48 samples and two out of the 10 patients had differences in blood results that might have had clinical implications. The telemonitoring system correctly generated 42 alerts. The patients found the telemonitoring system easy to use. With further refinement this should become an acceptable component of routine clinical practice for monitoring patients receiving chemotherapy. .
Alrifai, D.
Popat, S.
Ahmed, M.
Gonzalez, D.
Nicholson, A.G.
Parcq, J.D.
Benepal, T.
(2013). A rare case of squamous cell carcinoma of the lung harbouring ALK and BRAF activating mutations. Lung cancer,
Vol.80
(3),
pp. 339-340.
Lim, E.
Popat, S.
(2013). What exactly are we doing to improve low lung cancer survival in the United Kingdom?. Thorax,
Vol.68
(6),
pp. 504-505.
Papa, S.
Popat, S.
Shah, R.
Prevost, A.T.
Lal, R.
McLennan, B.
Cane, P.
Lang-Lazdunski, L.
Viney, Z.
Dunn, J.T.
Barrington, S.
Landau, D.
Spicer, J.
(2013). Phase 2 Study of Sorafenib in Malignant Mesothelioma Previously Treated with Platinum-Containing Chemotherapy. Journal of thoracic oncology,
Vol.8
(6),
pp. 783-787.
O’Brien, M.E.
Gaafar, R.M.
Popat, S.
Grossi, F.
Price, A.
Talbot, D.C.
Cufer, T.
Ottensmeier, C.
Danson, S.
Pallis, A.
Hasan, B.
Van Meerbeeck, J.P.
Baas, P.
(2013). Phase II study of first-line bortezomib and cisplatin in malignant pleural mesothelioma and prospective validation of progression free survival rate as a primary end-point for mesothelioma clinical trials (European Organisation for Research and Treatment of Cancer 08052). European journal of cancer,
Vol.49
(13),
pp. 2815-2822.
Balachandran, K.
Popat, S.
(2013). Endocrine manifestations of malignancy. Medicine,
Vol.41
(10),
pp. 570-572.
Früh, M.
De Ruysscher, D.
Popat, S.
Crinò, L.
Peters, S.
Felip, E.
(2013). Small-cell lung cancer (SCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of oncology,
Vol.24,
pp. vi99-vi105.
Yap, T.A.
Popat, S.
(2013). The role of afatinib in the management of non-small cell lung carcinoma. Expert opinion on drug metabolism & toxicology,
Vol.9
(11),
pp. 1529-1539.
Pender, A.
Coward, J.
Gunapala, R.
Brien, M.O.
Bhosle, J.
Popat, S.
(2013). OUTCOMES OF PATIENTS UNDERGOING ADJUVANT PLATINUM- VINORELBINE CHEMOTHERAPY FOR RESECTED NON- SMALL CELL LUNG CANCER (NSCLC). Journal of thoracic oncology,
Vol.8,
pp. S1168-S1168.
Le Quesne, J.
Maurya, M.
De Castro, D.G.
Popat, S.
Wotherspoon, A.
Nicholson, A.
(2013). A COMPARISON OF FISH AND IMMUNOHISTOCHEMISTRY IN THE DETECTION OF ALK REARRANGEMENT IN LUNG ADENOCARCINOMA. Journal of thoracic oncology,
Vol.8,
pp. S1085-S1086.
Freydina, D.V.
Tay, A.
Chudasama, D.
Freidin, M.B.
Nicholson, A.G.
Rice, A.
Montero-Fernandez, A.
Popat, S.
Anikin, V.
Lim, E.
(2013). DIAGNOSTIC PERFORMANCE OF A FILTER-BASED ANTIBODY-INDEPENDENT PERIPHERAL BLOOD CIRCULATING TUMOUR CELL CAPTURE PAIRED WITH CYTOMORPHOLOGIC CRITERIA FOR THE DIAGNOSIS OF LUNG CANCER. Journal of thoracic oncology,
Vol.8,
pp. S1278-S1278.
Lim, E.
De Castro, D.G.
Popat, S.
Shaw, E.
Walker, I.
Johnson, P.
Bamsey, O.
Higgins, A.
Osadolor, T.
Renouf, L.
Nicholson, A.G.
(2013). FREQUENCY IN EGFR, K-RAS, BRAF AND ALK MUTATIONS IN A COHORT OF CANCERS: ALK TRANSLOCATIONS ARE MORE FREQUENTLY SEEN IN ADVANCED DISEASE. Journal of thoracic oncology,
Vol.8,
pp. S1222-S1223.
de Mello, R.A.
Madureira, P.
Carvalho, L.S.
Araújo, A.
O’Brien, M.
Popat, S.
(2013). EGFR and KRAS mutations, and ALK fusions: current developments and personalized therapies for patients with advanced non-small-cell lung cancer. Pharmacogenomics,
Vol.14
(14),
pp. 1765-1777.
show abstract
Personalized therapy has significantly developed in lung cancer treatment over recent years. VEGF and EGF play a major role in non-small-cell lung cancer (NSCLC) tumor angiogenesis and aggressiveness. EGFR mutation as well as KRAS and ALK rearrangements are important biomarkers in the field owing to potential targeted therapies involved in clinical practice: erlotinib, geftinib, cetuximab and crizotinib. More recently, regulation of tumor immunity through CTLA4 and PD1/L1 has emerged as a promising field in NSCLC management. This review will focus on the current and future biomarkers in the advanced NSCLC field and also address potential related targeted therapies for these patients. .
Gennatas, S.
Stanway, S.J.
Thomas, R.
Min, T.
Shah, R.
O’Brien, M.E.
Popat, S.
(2013). Early pneumothorax as a feature of response to crizotinib therapy in a patient with ALK rearranged lung adenocarcinoma. Bmc cancer,
Vol.13
(1).
Pender, A.
Letsa, I.
Reid, A.
Waddell, T.
Nimako, K.
Tan, D.
Xynos, I.
Ayite, B.
Priest, K.
Watson, S.
Stewart, Z.
Severn, J.
Popat, S.
O'Brien, M.
(2012). 21 Weekly paclitaxel and three weekly docetaxel appear active and well-tolerated in third and fourth-line advanced NSCLC patients. Lung cancer,
Vol.75,
pp. S7-S7.
Myerson, J.
O'Brien, M.
Waddell, T.
Reid, A.
Gunapala, R.
Starling, N.
Seet, J.E.
Nimako, K.
Popat, S.
(2012). 76 The UK ‘two week rule’ for lung cancer – 5-year survival update. Lung cancer,
Vol.75,
pp. S25-S26.
Tai, F.W.
Khor, K.S.
Popat, S.
Beckles, M.
Leung, M.
Lim, E.
(2012). 36 Oncologists', physicians' and surgeons' opinions on the perceived value and appropriateness of the speciality to inform patients on adjuvant chemotherapy after radical surgery for non-small cell lung cancer. Lung cancer,
Vol.75,
pp. S12-S12.
Leary, A.F.
Castro, D.G.
Nicholson, A.G.
Ashley, S.
Wotherspoon, A.
O’Brien, M.E.
Popat, S.
(2012). Establishing an EGFR mutation screening service for non-small cell lung cancer – Sample quality criteria and candidate histological predictors. European journal of cancer,
Vol.48
(1),
pp. 61-67.
Freidin, M.
Nicholson, A.
Popat, S.
Moffatt, M.
Cookson, W.
Lim, E.
(2012). 6 Distribution profile of baseline gene expression to standardise tumour expression: a pilot study of cisplatin resistant genes in lung cancer. Lung cancer,
Vol.75,
pp. S2-S3.
Coward, J.I.
Nathavitharana, R.
Popat, S.
(2012). True hypoglycaemia secondary to treatment with granulocyte colony stimulating factor (G-CSF) in a diabetic patient with non-small cell lung cancer. Lung cancer,
Vol.75
(1),
pp. 133-135.
O’Brien, M.E.
Myerson, J.S.
Coward, J.I.
Puglisi, M.
Trani, L.
Wotherspoon, A.
Sharma, B.
Cook, G.
Ashley, S.
Gunapala, R.
Chua, S.
Popat, S.
(2012). A phase II study of 18F-fluorodeoxyglucose PET–CT in non-small cell lung cancer patients receiving erlotinib (Tarceva®); objective and symptomatic responses at 6 and 12weeks. European journal of cancer,
Vol.48
(1),
pp. 68-74.
Popat, S.
Gonzalez, D.
Min, T.
Swansbury, J.
Dainton, M.
Croud, J.G.
Rice, A.J.
Nicholson, A.G.
(2012). ALK translocation is associated with ALK immunoreactivity and extensive signet-ring morphology in primary lung adenocarcinoma. Lung cancer,
Vol.75
(3),
pp. 300-305.
Nimako, K.
Popat, S.
(2012). Management of lung cancer. Medicine,
Vol.40
(4),
pp. 202-207.
Coward, J.I.
Ding, N.-.
Feakins, R.
Kocher, H.
Popat, S.
Szlosarek, P.W.
(2012). Chemotherapy-induced bowel obstruction in small cell lung cancer: a case report. Medical oncology,
Vol.29
(4),
pp. 2623-2625.
O'Connor, S.J.
Elliott, S.
Chinegwundoh, J.
Popat, S.
Rhode, A.L.
(2011). 67 Retrospective audit of a district general hospital (DGH) lung multi-disciplinary team (MDT) - lessons from misses and near-misses of treatment deadline. Lung cancer,
Vol.71,
pp. S23-S23.
Okera, M.
Chan, S.
Dernede, U.
Larkin, J.
Popat, S.
Gilbert, D.
Jones, L.
Osuji, N.
Sykes, H.
Oakley, C.
Pickering, L.
Lofts, F.
Chowdhury, S.
(2011). A prospective study of chemotherapy-induced febrile neutropenia in the South West London Cancer Network Interpretation of study results in light of NCAG/NCEPOD findings. British journal of cancer,
Vol.104
(3),
pp. 407-412.
Popat, S.
Gonzalez, D.
Min, T.
Swansbury, J.
Dainton, M.
Croud, J.
Rice, A.
Nicholson, A.G.
(2011). ALK TRANSLOCATION IS ASSOCIATED WITH ALK IMMUNOREACTIVITY AND EXTENSIVE SIGNET-RING MORPHOLOGY IN PRIMARY LUNG ADENOCARCINOMA. Journal of thoracic oncology,
Vol.6
(6),
pp. S506-S507.
Leary, A.
Gonzalez, D.
Nicholson, A.G.
Wotherspoon, A.
Olansunkanmi, F.
O'Brien, M.
Popat, S.
(2011). SAMPLE QUALITY CRITERIA FOR ROUTINE EGFR MUTATION SCREENING - PATHOLOGICAL FEATURES MAY BE MORE USEFUL THAN CLINICAL PHENOTYPE IN A UK POPULATION. Journal of thoracic oncology,
Vol.6
(6),
pp. S569-S570.
Pattenden, H.
Deshmukh, M.
Dusmet, M.
Goldstraw, P.
Lim, E.
Jordan, S.
Ladas, G.
Popat, S.
Rice, A.
Von der Thusen, J.
Nicholson, A.G.
(2011). PERIPHERAL VERSUS CENTRAL RESECTED PRIMARY SQUAMOUS CELL CARCINOMAS OF THE LUNG - A REVIEW OF 526 CASES. Journal of thoracic oncology,
Vol.6
(6),
pp. S445-S446.
Waddell, T.S.
Myerson, J.
Reid, A.
Ashley, S.
Starling, N.
Seet, J.-.
Nimako, K.
Popat, S.
O'Brien, M.E.
(2011). THE UK TWO WEEK RULE INITIATIVE IN LUNG CANCER - FIRST REPORT OF IMPACT ON DISEASE STAGE AND 5-YEAR SURVIVAL. Journal of thoracic oncology,
Vol.6
(6),
pp. S523-S524.
Popat, S.
Riley, R.D.
Billingham, L.J.
Hubner, R.A.
(2011). EXCISION REPAIR CROSS-COMPLEMENTATION GROUP 1 (ERCC1) STATUS AND NON-SMALL CELL LUNG CANCER (NSCLC) OUTCOMES: A META-ANALYSIS OF PUBLISHED STUDIES AND RECOMMENDATIONS. Journal of thoracic oncology,
Vol.6
(6),
pp. S438-S439.
Myerson, J.S.
Nimako, K.
Moore, S.
Karpathakis, A.
Calderone, R.
Popat, S.
O'Brien, M.
(2011). QUALITY OF LIFE ASSESSMENTS IN LUNG CANCER AND MESOTHELIOMA A COMPARISON OF QUESTIONNAIRES AND PHYSICIAN CONSULTATION - A POOR WORKMAN ALWAYS BLAMES HIS TOOLS?. Journal of thoracic oncology,
Vol.6
(6),
pp. S1206-S1207.
Tai, F.W.
Khor, K.S.
Popat, S.
Beckles, M.
Leung, M.
Al-Sahaf, M.
Lim, E.
(2011). ONCOLOGISTS, PHYSICIANS AND SURGEONS OPINIONS ON THE PERCEIVED VALUE AND APPROPRIATENESS OF THE SPECIALITY TO INFORM PATIENTS ON ADJUVANT CHEMOTHERAPY AFTER RADICAL SURGERY FOR NON-SMALL CELL LUNG CANCER. Journal of thoracic oncology,
Vol.6
(6),
pp. S1334-S1334.
Myerson, J.S.
Nimako, K.
Ranu, H.
Madden, B.
Popat, S.
O'Brien, M.
(2011). RANDOMISED EVALUATION OF STENTS TO OPEN RESTRICTED AIRWAYS IN PATIENTS WITH CENTRALLY PLACED NON-SMALL CELL LUNG CANCER (RESTORE - AIR). Journal of thoracic oncology,
Vol.6
(6),
pp. S1201-S1202.
Reid, A.
Waddell, T.S.
Nimako, K.
Tan, D.
Xynos, I.
Popat, S.
O'Brien, M.E.
(2011). WEEKLY PACLITAXEL APPEARS ACTIVE AND WELL-TOLERATED IN THIRD AND FOURTH-LINE ADVANCED NSCLC PATIENTS. Journal of thoracic oncology,
Vol.6
(6),
pp. S1301-S1301.
Freidin, M.B.
Bhudia, N.
Lim, E.
Nicholson, A.G.
Popat, S.
Cookson, W.O.
Moffatt, M.F.
(2011). SAMPLE HANDLING AND PROCESSING ARE CRITICAL FACTORS INFLUENCING THE RESULTS OF WHOLE GENOME GENE EXPRESSION PROFILING IN LUNG CANCER TISSUES. Journal of thoracic oncology,
Vol.6
(6),
pp. S373-S374.
Patton, S.
Thunnissen, E.
Murray, S.
Benlloch, S.
Butler, R.
Dietel, M.
Filipits, M.
Kerr, K.M.
Normanno, N.
Popat, S.
Wallace, A.
Stahel, R.
Taron, M.
Blackhall, F.
(2011). A PILOT EXTERNAL QUALITY ASSURANCE SCHEME FOR SOMATIC EGFR MUTATION TESTING IN NON-SMALL CELL LUNG CANCER. Journal of thoracic oncology,
Vol.6
(6),
pp. S1510-S1511.
Calderone, R.
Nimako, K.
Leary, A.
Popat, S.
O’Brien, M.E.
(2011). Under usage of zoledronic acid in non-small cell lung cancer patients with metastatic bone disease – a short communication. European journal of cancer,
Vol.47
(11),
pp. 1603-1605.
Hubner, R.A.
Goldstein, R.
Mitchell, S.
Jones, A.
Ashley, S.
O’Brien, M.E.
Popat, S.
(2011). Influence of co-morbidity on renal function assessment by Cockcroft–Gault calculation in lung cancer and mesothelioma patients receiving platinum-based chemotherapy. Lung cancer,
Vol.73
(3),
pp. 356-360.
Popat, S.
Vieira de Araújo, A.
Min, T.
Swansbury, J.
Dainton, M.
Wotherspoon, A.
Lim, E.
Nicholson, A.G.
O'Brien, M.E.
(2011). Lung Adenocarcinoma with Concurrent Exon 19 EGFR Mutation and ALK Rearrangement Responding to Erlotinib. Journal of thoracic oncology,
Vol.6
(11),
pp. 1962-1963.
Dong-bing, Z.
Chandler, I.
Zheng-ming, C.
Hong-chao, P.
Popat, S.
Yong-fu, S.
Houlston, R.S.
(2011). Mismatch repair, minichromosome maintenance complex component 2, cyclin A, and transforming growth factor beta receptor type II as prognostic factors for colorectal cancer: results of a 10-year prospective study using tissue microarray analysis. Chinese medical journal,
Vol.124
(4),
pp. 483-490.
Khor, K.S.
Tai, D.
Popat, S.
Beckles, M.
Leung, M.
Al Sahaf, M.
Lim, E.K.
(2011). Oncologists', physicians' and surgeons' opinions on the perceived value and appropriateness of the speciality to inform patients on adjuvant chemotherapy after radical surgery for non-small cell lung cancer. J clin oncol,
Vol.29
(15_suppl),
p. 7011.
show abstract
7011 Background: The benefit of chemotherapy after surgery for lung cancer is established, but roles and responsibilities of discussing adjuvant chemotherapy are not established. Whilst risks are straight forward to convey, difficulties in conveying the benefit results from published hazard ratios as the benefit varies with stage and therefore needs to be calculated individually and conveyed in a language that is understood by the patient. METHODS: From 2010 to 2011, a survey was conducted of cancer physicians, oncologists and surgeons in the UK. Clinicians asked to rank the most appropriate speciality to discuss adjuvant chemotherapy with patients, to calculate expected survival given baseline survival probability of 80% and a hazard ratio of 0.80, and then surveyed for the additional expected gain in cohorts with a 5 year survival probability of 40%, 60% and 80% respectively before they would recommend adjuvant chemotherapy Results: A total of 202 responses were received from 27 surgeons, 77 physicians, 87 oncologists (11 unstated). The majority of 56% of surgeons, 79% of physicians and 61% of oncologists felt an oncologist as the most appropriate initial clinician to discuss adjuvant chemotherapy with patients after surgery. In total 33% of surgeons, 53% of physicians and 73% of oncologists were able to correctly calculate the expected survival of patients. When asked about perceived value before considering recommending adjuvant chemotherapy with 5 year survival probabilities of 40%, 60% and 80%, clinicians reported an expected a mean gain (SE) of 20.8% (2.7), 15.6% (2.4) and 13.2% (2.1) against an expected of 12%, 8% and 4% respectively with a hazard ratio of 0.80. CONCLUSIONS: Our survey suggest oncologists as the clinicians best able to calculate the individual benefit of adjuvant chemotherapy and the majority of specialities polled agreed oncologists as the most appropriate initial person to discuss adjuvant chemotherapy with patients after radical surgery for lung cancer. The perceived value prior to recommending adjuvant chemotherapy in clinicians greatly exceeds current published results..
Khor, K.S.
Tai, D.
Popat, S.
Beckles, M.
Leung, M.
Al Sahaf, M.
Lim, E.K.
(2011). Oncologists', physicians' and surgeons' opinions on the perceived value and appropriateness of the speciality to inform patients on adjuvant chemotherapy after radical surgery for non-small cell lung cancer. Journal of clinical oncology,
Vol.29
(15_suppl),
pp. 7011-7011.
Goldstein, R.
Reid, F.
Campbell, J.
Popat, S.
Benepal, T.
(2010). Neurosurgery for brain metastases (BM) in the management of non-small cell lung cancer (NSCLC): A retrospective study of all cerebral metastasectomies at St George's Hospital London (SGH), 1999–2009. Lung cancer,
Vol.67,
pp. S38-S38.
Hubner, R.
Goldstein, R.
Mitchell, S.
Jones, A.
Ashley, S.
O'Brien, M.
Popat, S.
(2010). Influence of co-morbidity on renal function estimation by Cockcroft Gault calculation in lung cancer and mesothelioma patients receiving platinum-based chemotherapy. Lung cancer,
Vol.67,
pp. S9-S9.
Lim, E.
Baldwin, D.
Beckles, M.
Duffy, J.
Entwisle, J.
Faivre-Finn, C.
Kerr, K.
Macfie, A.
McGuigan, J.
Padley, S.
Popat, S.
Screaton, N.
Snee, M.
Waller, D.
Warburton, C.
Win, T.
(2010). Guidelines on the radical management of patients with lung cancer. Thorax,
Vol.65
(Suppl 3),
pp. iii1-iii27.
Forster, M.
Enting, D.
Nicholson, A.G.
O’Brien, M.
Popat, S.
(2010). The combination of Young's syndrome and small cell lung cancer—A spiky connection?. Lung cancer,
Vol.67
(3),
pp. 372-375.
Nicholson, A.G.
Gonzalez, D.
Shah, P.
Pynegar, M.J.
Deshmukh, M.
Rice, A.
Popat, S.
(2010). Refining the Diagnosis and EGFR Status of Non-small Cell Lung Carcinoma in Biopsy and Cytologic Material, Using a Panel of Mucin Staining, TTF-1, Cytokeratin 5/6, and P63, and EGFR Mutation Analysis. Journal of thoracic oncology,
Vol.5
(4),
pp. 436-441.
Calderone, R.G.
Nimako, K.
Leary, A.N.
Popat, S.
Kipps, E.
O'Brien, M.N.
(2010). USE OF ZOLEDRONIC ACID IN LUNG CANCER. Journal of thoracic oncology,
Vol.5
(5),
pp. S99-S100.
Brunetto, A.T.
Carden, C.P.
Myerson, J.
Faria, A.L.
Ashley, S.
Popat, S.
O'Brien, M.E.
(2010). Modest Reductions in Dose Intensity and Drug-Induced Neutropenia have No Major Impact on Survival of Patients with Non-small Cell Lung Cancer Treated with Platinum-Doublet Chemotherapy. Journal of thoracic oncology,
Vol.5
(9),
pp. 1397-1403.
Myerson, J.S.
Iqbal, S.A.
O’Brien, M.E.
Popat, S.
(2010). Supersensitive Mutation: Two Case Reports of Non–Small-Cell Lung Cancer Treated With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors. Clinical lung cancer,
Vol.11
(5),
pp. E5-E8.
Myerson, J.S.
Faria, A.
Puglisi, M.
Starling, N.
Popat, S.
O’Brien, M.E.
(2010). The value of day 8 blood count in treatment decisions when using oral vinorelbine in non-small cell lung cancer. Lung cancer,
Vol.69
(3),
pp. 365-366.
Trani, L.
Myerson, J.
Ashley, S.
Young, K.
Sheri, A.
Hubner, R.
Puglisi, M.
Popat, S.
O’Brien, M.E.
(2010). Histology classification is not a predictor of clinical outcomes in advanced non-small cell lung cancer (NSCLC) treated with vinorelbine or gemcitabine combinations. Lung cancer,
Vol.70
(2),
pp. 200-204.
Puglisi, M.
Dolly, S.
Faria, A.
Myerson, J.S.
Popat, S.
O'Brien, M.E.
(2010). Treatment options for small cell lung cancer – do we have more choice?. British journal of cancer,
Vol.102
(4),
pp. 629-638.
Irshad, S.
Popat, S.
Shah, R.N.
Burbridge, S.
Lal, R.
Lang-Lazdunski, L.
Viney, Z.
Marsden, P.
Barrington, S.
Spicer, J.F.
(2010). A phase II study of sorafenib in malignant mesothelioma with pharmacodynamic imaging using 18fdg-PET. Journal of clinical oncology,
Vol.28
(15_suppl),
pp. 7038-7038.
Benson, C.
Kristeleit, R.S.
Ashley, S.
Dolly, S.
Mikropoulos, C.
O'Brien, M.
Popat, S.
(2010). Retrospective review of all patients with thymoma treated over the last 33 years at the Royal Marsden Hospital. Journal of clinical oncology,
Vol.28
(15_suppl),
pp. 7095-7095.
Myerson, J.S.
Moore, S.A.
Popat, S.
O'Brien, M.E.
(2010). Quality of Life Assessments in Lung Cancer - An evaluation of three questionnaires What's best for routine clinical practice?. American journal of respiratory and critical care medicine,
Vol.181.
Benning, J.
Starling, N.
Myerson, J.S.
Popat, S.
Ashley, S.
O'Brien, M.E.
(2009). An audit of neutropaenia in patients with small cell lung carcinoma (SCLC) undergoing platinum-based chemotherapy – urgent need for specific SCLC guidelines. Lung cancer,
Vol.63,
pp. S13-S13.
Faria, A.
Myerson, J.S.
Puglisi, M.
Starling, N.
Ashley, S.
Popat, S.
O'Brien, M.E.
Bruzynski, P.
(2009). The value of day 8 blood count in treatment decisions when using oral vinorelbine in non-small cell lung cancer (NSCLC) patients. Lung cancer,
Vol.63,
pp. S4-S4.
Baird, R.
Mikropoulos, C.
Ashley, S.
Killick, E.
Myerson, J.S.
Wotherspoon, A.
O'Brien, M.E.
Popat, S.
Jackson-Jones, R.
(2009). Audit of epidermal growth factor receptor (EGFR) expression by immunohistochemistry (IHC) using Dako and Ventana clones in non-small cell lung cancer (NSCLC). Lung cancer,
Vol.63,
pp. S2-S3.
Dolly, S.O.
Popat, S.
(2009). Endocrine manifestations of malignancy. Medicine,
Vol.37
(9),
pp. 457-460.
O'Brien, M.E.
Myerson, J.S.
Popat, S.
Puglisi, M.
Starling, N.
Trani, L.
Bhupinder, S.
Gary, C.
Sue, A.
(2009). The use of PET-CT scan in the assessment of response to Tarceva (erlotinib) in non small cell lung (NSCLC) cancer patients. Journal of thoracic oncology,
Vol.4
(9),
pp. S390-S391.
Popat, S.
Barbachano, Y.
Ashley, S.
Norton, A.
O’Brien, M.
(2008). Erlotinib, docetaxel, and gefitinib in sequential cohorts with relapsed non-small cell lung cancer. Lung cancer,
Vol.59
(2),
pp. 227-231.
Hughes, S.
Barbachano, Y.
Ashley, S.
Yap, Y.-.
Popat, S.
Allen, M.
Della-Rovere, U.Q.
Johnston, S.
Smith, I.
O’Brien, M.
(2008). Time Trends in the Outcome of Elderly Patients with Breast Cancer. The breast journal,
Vol.14
(2),
pp. 158-163.
O'Brien, M.E.
Yau, T.
Coward, J.
Hughes, S.
Papadopoulos, P.
Popat, S.
Norton, A.
Ashley, S.
(2008). Time and Chemotherapy Treatment Trends in the Treatment of Elderly Patients (Age≥70 Years) with Non-small Cell Lung Cancer. Clinical oncology,
Vol.20
(2),
pp. 142-147.
Brunetto, A.
Carden, C.P.
Ashley, S.
Baird, R.
Myerson, J.
Kristeleit, R.
Montes, A.
Popat, S.
O'Brien, M.
(2008). Dose intensity in advanced non-small cell lung cancer. Lung cancer,
Vol.60,
pp. S20-S20.
Ho, G.F.
Popat, S.
Nutting, C.
(2008). Induction and concurrent chemoradiotherapy for non-small cell lung cancer (NSCLC) using cisplatin and vinorelbine. Lung cancer,
Vol.60,
pp. S18-S18.
Carden, C.P.
Myerson, J.S.
Popat, S.
Montes, A.
Larkin, J.M.
Benson, M.J.
O'Brien, M.E.
(2008). Good Vibrations and the Power of Positron Thinking: Positron Emission Tomography and Endoscopic Ultrasound in Staging of Mesothelioma—Two Case Reports. Journal of thoracic oncology,
Vol.3
(5),
pp. 539-541.
Popat, S.
Smith, I.E.
(2008). Therapy Insight: anthracyclines and trastuzumab—the optimal management of cardiotoxic side effects. Nature clinical practice oncology,
Vol.5
(6),
pp. 324-335.
Sirohi, B.
Arnedos, M.
Popat, S.
Ashley, S.
Nerurkar, A.
Walsh, G.
Johnston, S.
Smith, I.E.
(2008). Platinum-based chemotherapy in triple-negative breast cancer. Annals of oncology,
Vol.19
(11),
pp. 1847-1852.
Drilon, A.D.
Popat, S.
Bhuchar, G.
D'Adamo, D.R.
Keohan, M.L.
Fisher, C.
Antonescu, C.R.
Singer, S.
Brennan, M.F.
Judson, I.
Maki, R.G.
(2008). Extraskeletal myxoid chondrosarcoma: a retrospective review from 2 referral centers emphasizing long-term outcomes with surgery and chemotherapy. Cancer,
Vol.113
(12),
pp. 3364-3371.
show abstract
Extraskeletal myxoid chondrosarcoma (EMC) is a genetically distinct sarcoma with a propensity for local recurrence and metastasis despite an indolent course. To the authors' knowledge, there are limited data examining chemotherapy outcomes as a guide to therapeutic decisions for unresectable disease..
Sirohi, B.
Arnedos, M.
Popat, S.
Ashley, S.
Nerurkar, A.
Walsh, G.
Johnston, S.
Smith, I.E.
(2008). Platinum-based chemotherapy in triple-negative (TN) breast cancer. Journal of clinical oncology,
Vol.26
(15_suppl),
pp. 1051-1051.
Dernedde, U.
Chan, S.
Sykes, H.
Oakley, C.
Larkin, J.
Popat, S.
Gilbert, D.
Jones, L.
Chowdhury, S.
(2008). South West London Cancer Network (SWLCN) audit of patients with chemotherapy-induced febrile neutropenia (CIFN). Journal of clinical oncology,
Vol.26
(15_suppl),
pp. 20653-20653.
Tjellström, B.
Stenhammar, L.
Högberg, L.
Fälth-Magnusson, K.
Magnusson, K.-.
Midtvedt, T.
Sundqvist, T.
Houlston, R.
Popat, S.
Norin, E.
(2007). Gut microflora associated characteristics in first-degree relatives of children with celiac disease. Scandinavian journal of gastroenterology,
Vol.42
(10),
pp. 1204-1208.
Popat, S.
Zhao, D.B.
Chen, Z.M.
Pan, H.C.
Sha, Y.F.
Chandler, I.
Houlston, R.S.
(2007). Relationship between chromosome 18q status and colorectal cancer prognosis: A prospective, blinded analysis of 280 patients (vol 27, pg 627, 2007). Anticancer research,
Vol.27
(2),
pp. 1231-1.
Popat, S.
Hughes, S.
Papadopoulos, P.
Wilkins, A.
Moore, S.
Priest, K.
Meehan, L.
Norton, A.
O’Brien, M.
(2007). Recurrent responses to non-small cell lung cancer brain metastases with erlotinib. Lung cancer,
Vol.56
(1),
pp. 135-137.
Sirohi, B.
Ashley, S.
Norton, A.
Popat, S.
Hughes, S.
Papadopoulos, P.
Priest, K.
O'Brien, M.
(2007). Early Response to Platinum-Based First-Line Chemotherapy in Non-small Cell Lung Cancer May Predict Survival. Journal of thoracic oncology,
Vol.2
(8),
pp. 735-740.
Wilkins, A.
Popat, S.
Hughes, S.
O’Brien, M.
(2007). Malignant pleural mesothelioma: Two cases in first degree relatives. Lung cancer,
Vol.57
(3),
pp. 407-409.
Popat, S.
Zhao, D.
Chen, Z.
Pan, H.
Shao, Y.
Chandler, I.
Houlston, R.S.
(2007). Relationship between chromosome 18q status and colorectal cancer prognosis: A prospective, blinded analysis of 280 patients. Anticancer research,
Vol.27
(1B),
pp. 627-633.
Hubner, R.A.
Muir, K.R.
Liu, J.-.
Logan, R.F.
Grainge, M.
Armitage, N.
Shepherd, V.
Popat, S.
Houlston, R.S.
(2006). Genetic Variants of UGT1A6 Influence Risk of Colorectal Adenoma Recurrence. Clinical cancer research,
Vol.12
(21),
pp. 6585-6589.
show abstract
Abstract
Purpose: The UDP glucuronosyltransferase 1A6 (UGT1A6) and cytochrome P450 2C9 (CYP2C9) enzymes participate in the metabolism of nonsteroidal anti-inflammatory drugs, endogenous substances, and carcinogens. Functional polymorphisms of UGT1A6 (T181A and R184S) and CYP2C9 (R144C and I359L) have been reported to modify the protective effect of aspirin on colorectal adenoma risk. We aimed to further investigate the effect of these genetic variants on the development of colorectal neoplasia.
Experimental Design: We examined the relationship between UGT1A6 and CYP2C9 genotype and colorectal adenoma recurrence in 546 patients participating in a randomized placebo-controlled aspirin intervention trial.
Results: Although colorectal adenoma recurrence was not significantly influenced by CYP2C9 genotype, carriers of variant UGT1A6 alleles were at significantly reduced risk of colorectal neoplasia recurrence [relative risk (RR), 0.68; 95% confidence interval (95% CI), 0.52-0.89]. This risk reduction was also evident when the analysis was confined to advanced neoplasia recurrence (RR, 0.71; 95% CI, 0.47-1.09). When patients were stratified by genotype and aspirin intervention, those with variant UGT1A6 alleles were at reduced recurrence risk irrespective of whether they received aspirin or placebo (RR, 0.62; 95% CI, 0.42-0.92 and RR, 0.63; 95% CI, 0.44-0.91, respectively).
Conclusions: These findings confirm that UGT1A6 variants influence colorectal carcinogenesis independent of aspirin intake and suggest that they may have clinical value in secondary prevention programs for patients diagnosed with colorectal adenoma..
Yau, T.
Ashley, S.
Popat, S.
Norton, A.
Matakidou, A.
Coward, J.
O'Brien, M.E.
(2006). Time and chemotherapy treatment trends in the treatment of elderly patients (age ⩾70 years) with small cell lung cancer. British journal of cancer,
Vol.94
(1),
pp. 18-21.
Popat, S.
Smith, I.E.
(2006). Breast cancer. Update on cancer therapeutics,
Vol.1
(2),
pp. 187-210.
Popat, S.
Lopez, J.
Chan, S.
Waters, J.
Rutter, D.
E Hill, M.
(2006). Palliative treatments for patients with inoperable gastroesophageal cancers. International journal of palliative nursing,
Vol.12
(7),
pp. 306-317.
show abstract
Most patients with cancers of the stomach, oesophagus or gastroesophageal junction ultimately develop metastatic or inoperable disease, rendering them incurable. They can, however, benefit from a variety of palliative interventions inving the multidisciplinary team, including chemotherapy, radiotherapy, endoluminal stenting, laser, or surgery. Often a combination of such strategies will be used to control symptoms, and maintain or improve quality of life. In this article, we review these multidisciplinary interventional approaches in patients with gastroesophageal cancers, and highlight future trends. .
Popat, S.
Chen, Z.
Zhao, D.
Pan, H.
Hearle, N.
Chandler, I.
Shao, Y.
Aherne, W.
Houlston, R.S.
(2006). A prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer. Annals of oncology,
Vol.17
(12),
pp. 1810-1817.
Popat, S.
Wort, R.
Houlston, R.S.
(2006). Inter-relationship between microsatellite instability, thymidylate synthase expression, and p53 status in colorectal cancer: implications for chemoresistance. Bmc cancer,
Vol.6
(1).
show abstract
Abstract
Background
Studies indicate that thymidylate synthase (TS) expression, p53 and mismatch repair status have potential to influence colorectal cancer (CRC) outcome. There is, however, little data on the inter-relationship between these three markers. We sought to investigate whether relationships exist between these markers that might contribute to CRC phenotypes.
Methods
Four hundred and forty-one stage I-III CRCs were investigated. p53 status and TS expression were assessed by standard immunohistochemistry methods. Mismatch repair status was determined by assessment of microsatellite instability (MSI) using radiolabelled microsatellite genotyping.
Results
244 tumours (55%) over-expressed p53, and 259 (58%) expressed high TS levels. 65 tumours (15%) had MSI. A significant relationship between p53 over-expression and high TS expression was observed (p = 0.01). This was independent of MSI status. A highly significant inverse relationship between MSI and p53 status was observed (p = 0.001). No relationship was seen between MSI status and TS expression (p = 0.59).
Conclusion
Relationships exist between p53 status and TS expression, and MSI and p53 status. These inter-relationships may contribute to the clinical phenotype of CRCs associated with each of the molecular markers. High TS expression is unlikely to account for the clinical behaviour of CRCs with MSI.
.
Johnson, V.
(2005). Exon 3 -catenin mutations are specifically associated with colorectal carcinomas in hereditary non-polyposis colorectal cancer syndrome. Gut,
Vol.54
(2),
pp. 264-267.
Popat, S.
Smith, I.E.
(2005). Re: Neoadjuvant Versus Adjuvant Systemic Treatment in Breast Cancer: A Meta-Analysis. Jnci: journal of the national cancer institute,
Vol.97
(11),
pp. 858-858.
Popat, S.
Wort, R.
Houlston, R.S.
(2005). Relationship Between Thymidylate Synthase (TS) Genotype and TS Expression: A Tissue Microarray Analysis of Colorectal Cancers. International journal of surgical pathology,
Vol.13
(2),
pp. 127-133.
show abstract
Response of colorectal cancers to 5-fluorouracil appears to be influenced by differences in thymidylate synthase (TS) expression. To explore the relationship between TS 5’ genotype and expression, we analyzed paired tumor and normal tissue from 87 colorectal cancers by tissue microarray. A trend to an association between TS genotype and expression was observed, but the correlation was weak. Although the 2R homozygote was preferentially associated with TS expression (p<0.03), no relationship was observed for the 3R homozygote (p=1.0). The relationship between 5’ TS genotype and TS expression is not simple. For clinical trials incorporating TS status, detection of TS expression in tumors by immunohistochemistry must still remain the benchmark over genotype. .
Popat, S.
O??Brien, M.
(2005). Chemotherapy strategies in the treatment of small cell lung cancer. Anti-cancer drugs,
Vol.16
(4),
pp. 361-372.
Popat, S.
Houlston, R.S.
(2005). A systematic review and meta-analysis of the relationship between chromosome 18q genotype, DCC status and colorectal cancer prognosis. European journal of cancer,
Vol.41
(14),
pp. 2060-2070.
Rini, B.I.
Small, E.J.
(2005). Biology and Clinical Development of Vascular Endothelial Growth Factor–Targeted Therapy in Renal Cell Carcinoma. Journal of clinical oncology,
Vol.23
(5),
pp. 1028-1043.
show abstract
Purpose To review the biology of renal cell carcinoma (RCC) leading to vascular endothelial growth factor (VEGF) overexpression and the clinical results of VEGF blockade in metastatic RCC. Methods A review of relevant published literature regarding VEGF, von Hippel-Lindau (VHL) gene inactivation and VEGF overexpression in RCC was performed. Further, a review of the mechanism, toxicity, and clinical development of VEGF-targeted therapy in metastatic RCC was undertaken. Results VEGF is the major proangiogenic protein that exerts a biologic effect through interaction with cellular receptors. The majority of sporadic clear-cell RCC tumors are characterized by VHL tumor suppressor gene inactivation. The resulting VHL gene silencing leads to VEGF overexpression. An antibody to VEGF (bevacizumab) has demonstrated a significant prolongation of time to disease progression compared with placebo in patients with metastatic RCC. Small molecules with inhibitory effects against the VEGF receptor have undergone initial clinical testing in metastatic RCC with substantial objective response rates. Conclusion Therapeutic targeting of VEGF in RCC has strong biologic rationale and preliminary clinical efficacy. Further investigation will determine the optimal timing, sequence, and utility of these agents in RCC. .
Popat, S.
Matakidou, A.
Houlston, R.S.
(2005). In Reply:. Journal of clinical oncology,
Vol.23
(9),
pp. 2108-2109.
Popat, S.
Houlston, R.S.
(2005). Re: Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK). Jnci: journal of the national cancer institute,
Vol.97
(24),
pp. 1855-1855.
POPAT, S.
(2005). Systematic review of microsatellite instability and colorectal cancer prognosis. J clin oncol,
Vol.23,
pp. 609-618.
Popat, S.
Matakidou, A.
Houlston, R.S.
(2004). Thymidylate Synthase Expression and Prognosis in Colorectal Cancer: A Systematic Review and Meta-Analysis. Journal of clinical oncology,
Vol.22
(3),
pp. 529-536.
show abstract
Purpose A number of studies have investigated the relationship between thymidylate synthase (TS) expression and survival in colorectal cancer (CRC) patients. Although most have reported poorer overall and progression-free survival with high TS expression, estimates of the hazard ratio (HR) between studies differ wildly. To derive a more precise estimate of the prognostic significance of TS expression, we have reviewed published studies and carried out a meta-analysis. Materials and Methods Twenty studies stratifying overall survival and/or progression-free survival in CRC patients by TS expression status were eligible for analysis. The principal outcome measure was the HR. Data from these studies were pooled using standard meta-analysis techniques. Results Thirteen studies investigated outcome in a total of 887 cases with advanced CRC, and seven studies investigated outcome in a total of 2,610 patients with localized CRC. A number of methods were used both to assess TS expression and to assign TS status. Sample sizes varied greatly, small sample sizes being a feature of the advanced disease studies. The combined HR estimate for overall survival (OS) was 1.74 (95% CI, 1.34 to 2.26) and 1.35 (95% CI, 1.07 to 1.80) in the advanced and adjuvant settings, respectively, but there was evidence of heterogeneity and possible publication bias. Conclusion Tumors expressing high levels of TS appeared to have a poorer OS compared with tumors expressing low levels. Additional studies with consistent methodology are needed to define the precise prognostic value of TS. .
Sumpter, K.
Harper-Wynne, C.
Yeoh, C.
Popat, S.
Ashley, S.
Norton, A.
O’Brien, M.
(2004). Is the second line data on the use of docetaxel in non-small cell lung cancer reproducible?. Lung cancer,
Vol.43
(3),
pp. 369-370.
Popat, S.
Nicholson, A.G.
Fisher, C.
Harmer, C.
Moskovic, E.
Murday, V.A.
Houlston, R.S.
(2004). Pulmonary Masses Presenting 11 Years after Abdominal Surgery. Respiration,
Vol.71
(3),
pp. 295-297.
Hodgson, S.V.
Popat, S.
(2003). Polymorphic sequence variants in medicine: a challenge and an opportunity. Clinical medicine,
Vol.3
(3),
pp. 260-264.
Popat, S.
Stone, J.
Houlston, R.S.
(2003). Allelic imbalance in colorectal cancer at the CRAC1 locus in early-onset colorectal cancer. Cancer genetics and cytogenetics,
Vol.145
(1),
pp. 70-73.
Popat, S.
(2002). Genome screening of coeliac disease. Journal of medical genetics,
Vol.39
(5),
pp. 328-331.
Popat, S.
Hearle, N.
Wixey, J.
Hogberg, L.
Bevan, S.
Lim, W.
Stenhammar, L.
Houlston, R.S.
(2002). Analysis of the CTLA4 Gene in Swedish Coeliac Disease Patients. Scandinavian journal of gastroenterology,
Vol.37
(1),
pp. 28-31.
Popat, S.
Hearle, N.
Bevan, S.
Hogberg, L.
Stenhammar, L.
Houlston, R.S.
(2002). Mutational Analysis of CD28 in Coeliac Disease. Scandinavian journal of gastroenterology,
Vol.37
(5),
pp. 536-539.
Popat, S.
Hearle, N.
Hogberg, L.
Braegger, C.P.
O'Donoghue, D.
Falth-Magnusson, K.
Holmes, G.K.
Howdle, P.D.
Jenkins, H.
Johnston, S.
Kennedy, N.P.
Kumar, P.J.
Logan, R.F.
Marsh, M.N.
Mulder, C.J.
Torinsson Naluai, A.
Sjoberg, K.
Stenhammar, L.
Walters, J.R.
Jewell, D.P.
Houlston, R.S.
(2002). Variation in the CTLA4/CD28 gene region confers an increased risk of coeliac disease. Annals of human genetics,
Vol.66
(Pt 2),
pp. 125-137.
show abstract
Susceptibility to coeliac disease involves HLA and non-HLA-linked genes. The CTLA4/CD28 gene region encodes immune regulatory T-cell surface molecules and is a strong candidate as a susceptibility locus. We evaluated CTLA4/CD28 in coeliac disease by genetic linkage and association and combined our findings with published studies through a meta-analysis. 116 multiplex families were genotyped across CTLA4/CD28 using eight markers. The contribution of CTLA4/CD28 to coeliac disease was assessed by non-parametric linkage and association analyses. Seven studies were identified that had evaluated the relationship between CTLA4/CD28 and coeliac disease and a pooled analysis of data undertaken. In our study there was evidence for a relationship between variation in the CTLA4/CD28 region and coeliac disease by linkage and association analyses. However, the findings did not attain formal statistical significance (p = 0.004 and 0.039, respectively). Pooling findings with published results showed significant evidence for linkage (504 families) and association (940 families): p values, 0.0001 and 0.0014 at D2S2214, respectively, and 0.0008 and 0.0006 at D2S116, respectively. These findings suggest that variation in the CD28/CTLA4 gene region is a determinant of coeliac disease susceptibility. Dissecting the sequence variation underlying this relationship will depend on further analyses utilising denser sets of markers..
Popat, S.
Hearle, N.
Bevan, S.
Holmes, G.K.
Howdle, P.D.
Hogberg, L.
Braegger, C.P.
O'Donoghue, D.
Falth-Magnusson, K.
Jenkins, H.
Johnston, S.
Kennedy, N.P.
Kumar, P.
Logan, R.F.
Marsh, M.N.
Mulder, C.J.
Sjoberg, K.
Stenhammar, L.
Walters, J.R.
Jewell, D.P.
Houlston, R.S.
(2002). A genetic analysis of coeliac disease. Gut,
Vol.50,
pp. A92-A92.
Popat, S.
Hogberg, L.
McGuire, S.
Green, H.
Bevan, S.
Stenhammar, L.
Houlston, R.S.
(2001). Germline mutations in TGM2 do not contribute to coeliac disease susceptibility in the Swedish population. European journal of gastroenterology & hepatology,
Vol.13
(12),
pp. 1477-1479.
Popat, S.
Stone, J.
Coleman, G.
Marshall, G.
Peto, J.
Frayling, I.
Houlston, R.
(2000). Prevalence of the APC E1317Q variant in colorectal cancer patients. Cancer letters,
Vol.149
(1-2),
pp. 203-206.
Bevan, S.
Popat, S.
Houlston, R.S.
(1999). Relative power of linkage and transmission disequilibrium test strategies to detect non-HLA linked coeliac disease susceptibility genes. Gut,
Vol.45
(5),
pp. 668-671.
Bevan, S.
Catovsky, D.
Marossy, A.
Matutes, E.
Popat, S.
Antonovic, P.
Bell, A.
Berrebi, A.
Gaminara, E.J.
Quabeck, K.
Ribeiro, I.
Mauro, F.R.
Stark, P.
Sykes, H.
van Dongen, J.
Wimperis, J.
Wright, S.
Yuille, M.R.
Houlston, R.S.
(1999). Linkage analysis for ATM in familial B cell chronic lymphocytic leukaemia. Leukemia,
Vol.13
(10),
pp. 1497-1500.
Bevan, S.
Popat, S.
Braegger, C.P.
Busch, A.
O'Donoghue, D.
Falth-Magnusson, K.
Ferguson, A.
Godkin, A.
Hogberg, L.
Holmes, G.
Hosie, K.B.
Howdle, P.D.
Jenkins, H.
Jewell, D.
Johnston, S.
Kennedy, N.P.
Kerr, G.
Kumar, P.
Logan, R.F.
Love, A.H.
Marsh, M.
Mulder, C.J.
Sjoberg, K.
Stenhammer, L.
Walker-Smith, J.
Marossy, A.M.
Houlston, R.S.
(1999). Contribution of the MHC region to the familial risk of coeliac disease. Journal of medical genetics,
Vol.36
(9),
pp. 687-690.
Brown, S.A.
Popat, S.
Carr, R.
(1997). An unusual cause of chest pain. Postgraduate medical journal,
Vol.73
(866),
pp. 825-827.
Matakidou, A.
Risk of non-medullary thyroid cancer influenced by polymorphic variation in the thyroglobulin gene. Carcinogenesis,
Vol.25
(3),
pp. 369-373.
Popat, S.
Yap, T.
Toward precision medicine with next-generation EGFR inhibitors in non-small-cell lung cancer. Pharmacogenomics and personalized medicine,
,
pp. 285-285.
True. Leukemia,
Vol.13
(10),
pp. 1497-1500.
Minchom, A.
Mak, D.
Gunapala, R.
Walder, D.
Kumar, R.
Yousaf, N.
Hodgkiss, A.
Bhosle, J.
Popat, S.
O'Brien, M.E.
A prospective observational study of on-treatment plasma homocysteine levels as a biomarker of toxicity, depression and vitamin supplementation lead-in time pre pemetrexed, in patients with non-small cell lung cancer and malignant mesothelioma. Plos one,
Vol.14
(11),
pp. e0225509-?.
show abstract
Objectives Vitamin supplementation reduces pemetrexed toxicity. Raised plasma homocysteine reflects deficiency in vitamin B12 and folate, and is suppressed by supplementation. This observational study of 112 patients receiving pemetrexed-based chemotherapy assessed homocysteine levels after 3 weeks of vitamin supplementation, hypothesising high levels would correlate with ongoing deficiency, thus increased toxicity.Material and methods Primary endpoint was the composite of proportion of patients with treatment delay/ dose reduction/ drug change or hospitalisation during the first six weeks of chemotherapy, comparing those with normal plasma homocysteine (successfully supplemented, SS) and those with high homocysteine (unsuccessfully supplemented, USS). Secondary endpoints included toxicity and analyses for depression. Post-hoc analysis examined correlation between interval of vitamin and folate supplementation and pemetrexed on primary endpoint and grade 3-4 toxicities.Results Eighty-four patients (84%) were successfully supplemented (SS group). The proportion of patients undergoing a treatment delay/ dose reduction/ drug change or hospitalisation in SS group was 44.0% (95% confidence interval [CI] 33.2%-55.3%) and in USS group was 18.8% (95% CI 4.0%-45.6%) (p = 0.09). Twelve percent of patients gave a past history of depression however 66% of patients had an on study Hospital Anxiety and Depression (HAD) score of >7. Supplementation status was not associated with depression. The median overall survival (OS) was 11.8 months (95% CI 8.6-16.5) in the SS group and 8.8 months (95% CI 6.6-16.2) in the US group (p = 0.5). The number of days (<7 or ≥ 7 days) between vitamin B12 and folate initiation and pemetrexed administration, had no effect on the primary endpoint and grade 3-4 toxicities.Conclusion On-treatment homocysteine levels were not a biomarker of toxicity or depression. Standard vitamin supplementation is adequate in the majority of patients receiving pemetrexed. High HAD score were noted in this population giving an opportunity for mental health intervention. The lead-in time for vitamin supplementation can be short..
Hubner, R.A.
Riley, R.D.
Billingham, L.J.
Popat, S.
Excision Repair Cross-Complementation Group 1 (ERCC1) Status and Lung Cancer Outcomes: A Meta-Analysis of Published Studies and Recommendations. Plos one,
Vol.6
(10),
pp. e25164-e25164.
Garcia Campelo, M.R.
Lin, H.M.
Zhu, Y.
Pérol, M.
Jahanzeb, M.
Popat, S.
Zhang, P.
Camidge, D.R.
Health-related quality of life in the randomized phase III trial of brigatinib vs crizotinib in advanced ALK inhibitor-naive ALK + non-small cell lung cancer (ALTA-1L). Lung cancer (amsterdam, netherlands),
Vol.155,
pp. 68-77.
show abstract
Objective In ALTA-1 L, first-line brigatinib versus crizotinib significantly prolonged progression-free survival in advanced ALK-positive (ALK+) non-small cell lung cancer (NSCLC). We report health-related quality of life (HRQOL) outcomes from ALTA-1 L.Materials and methods HRQOL was assessed using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and lung cancer-specific module (QLQ-LC13). HRQOL time to worsening, change from baseline, and duration of improvement were analyzed.Results EORTC QLQ-C30 and QLQ-LC13 compliance was >90 % for both groups (n = 131 each). Brigatinib versus crizotinib significantly delayed time to worsening in the EORTC QLQ-C30 global health status (GHS)/QOL (median: 26.74 vs 8.31 months; hazard ratio [HR]: 0.70; 95 % CI: 0.49, 1.00; log-rank P = 0.0485); emotional functioning, social functioning, fatigue, nausea and vomiting, appetite loss, and constipation scales (log-rank P < 0.05); delays in time to worsening for the physical, role, and cognitive functioning scales were not statistically significant. Mean change from baseline showed greater improvement in GHS/QOL and most EORTC QLQ-C30 functional and symptom scales with brigatinib versus crizotinib. Among patients with GHS/QOL improvement, brigatinib had longer duration of improvement versus crizotinib (median: not reached vs 11.99 months); similar results were seen in the physical, role, emotional, and social functioning; fatigue; nausea and vomiting; and appetite loss scales. Median time to worsening in dyspnea (QLQ-LC13) was 23.98 versus 8.25 months (brigatinib vs crizotinib; HR: 0.64; 95 % CI: 0.39, 1.05).Conclusion Brigatinib significantly delayed time to worsening and prolonged duration of improvement in GHS/QOL versus crizotinib, supported by improvement in functional and symptom scores. These preliminary analyses suggest brigatinib is the first ALK inhibitor with better HRQOL versus another ALK inhibitor in ALK inhibitor-naive advanced ALK + NSCLC..
Popat, S.
Brustugun, O.T.
Cadranel, J.
Felip, E.
Garassino, M.C.
Griesinger, F.
Helland, Å.
Hochmair, M.
Pérol, M.
Bent-Ennakhil, N.
Kruhl, C.
Novello, S.
Real-world treatment outcomes with brigatinib in patients with pretreated ALK+ metastatic non-small cell lung cancer. Lung cancer (amsterdam, netherlands),
Vol.157,
pp. 9-16.
show abstract
Background The next-generation ALK inhibitor brigatinib is approved for use in patients with ALK inhibitor-naïve ALK-positive advanced NSCLC and in patients previously treated with crizotinib. A phase II trial showed that brigatinib is active in patients with ALK-positive metastatic NSCLC (mNSCLC) who had progressed on prior crizotinib (response rate 56 %, median PFS 16.7 months, median OS 34.1 months). We report final data from the UVEA-Brig study of brigatinib in ALK inhibitor-pretreated ALK-positive mNSCLC in clinical practice.Methods UVEA-Brig was a retrospective chart review of patients treated with brigatinib in Italy, Norway, Spain and the UK in an expanded access program. Adults with ALK-positive mNSCLC, including those with brain lesions, resistant to or intolerant of ≥1 prior ALK inhibitor and ECOG performance status ≤3 were eligible. Patients received brigatinib 180 mg once daily with a 7-day lead-in at 90 mg. The objectives were to describe patient characteristics, clinical disease presentation, treatment regimens used and clinical outcomes.Results Data for 104 patients (male: 43 %; median age: 53 [29-80] years; ECOG performance status 0/1/2/3: 41/41/10/5 %; brain/CNS metastases: 63 %) were analyzed. Patients had received a median of 2 (1-6) lines of systemic therapy prior to brigatinib (37.5 % received ≥3) and a median of 1 (1-5) lines of prior ALK inhibitor-containing therapy (crizotinib 83.6 %; ceritinib 50.0 %; alectinib 6.7 %; lorlatinib 4.8 %). At the time of analysis, 77 patients had discontinued brigatinib. Overall, the response rate was 39.8 %, median PFS was 11.3 (95 % CI:8.6-12.9) months and median OS was 23.3 (95 % CI: 16.0-NR) months. Four patients discontinued brigatinib treatment due to adverse events. 53 patients received systemic therapy after brigatinib, 42 with an ALK inhibitor (lorlatinib, n = 34).Conclusions These real-world data indicate the activity and tolerability of brigatinib in patients with ALK-positive mNSCLC who were more heavily pretreated than patients included in clinical trials..
Tomasik, B.
Bieńkowski, M.
Braun, M.
Popat, S.
Dziadziuszko, R.
Effectiveness and safety of immunotherapy in NSCLC patients with ECOG PS score ≥2 - Systematic review and meta-analysis. Lung cancer (amsterdam, netherlands),
Vol.158,
pp. 97-106.
show abstract
Background Immune checkpoint inhibitors (ICIs) are standard of care in advanced non-small cell lung cancer (NSCLC), however their status in patients with poor performance status (PS) is poorly defined. We aimed to evaluate the efficacy and safety of ICIs in NSCLC patients with PS ≥ 2. Methods We conducted a systematic review and meta-analysis of interventional and observational studies, which reported efficacy and safety data on ICIs in PS ≥ 2 comparing to PS ≤ 1 NSCLC patients. Efficacy endpoints included: Objective Response Rate (ORR), Disease-Control Rate (DCR), Overall Survival (OS), Progression-Free Survival (PFS). Safety endpoint was the incidence of severe (grade≥3) Adverse Events (AE). Random-effects model was applied for meta-analysis. Heterogeneity was assessed using I 2 . The review is registered on PROSPERO (CRD42020162668). Findings Sixty-seven studies (n = 26,442 patients) were included. In PS ≥ 2 vs. PS ≤ 1 patients, the pooled odds ratios were: for ORR 0.46 (95 %CI: 0.39-0.54, I 2 :0 %); for DCR 0.39 (95 %CI: 0.33-0.48, I 2 :50 %) and for AEs 1.12 (95 %CI: 0.84-1.48, I 2 :39 %). The pooled hazard ratio for PFS was 2.17 (95 %CI: 1.96-2.39, I 2 :65 %) and for OS was 2.76 (95 %CI: 2.43-3.14, I 2 :76 %). The safety profile was comparable regardless of the PS status. Interpretation Patients with impaired PS status are, on average, twice less likely to achieve a response when exposed to ICIs when compared with representative PS ≤ 1 population. For lung cancer patients treated with ICIs, the impaired PS is not only prognostic, but also predictive for response, while the safety profile is not affected. Prospective randomized studies are indispensable to determine whether poor PS patients derive benefit from ICIs..
Popat, S.
Liu, G.
Lu, S.
Song, G.
Ma, X.
Yang, J.C.
Brigatinib vs alectinib in crizotinib-resistant advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer (ALTA-3). Future oncology (london, england),
Vol.17
(32),
pp. 4237-4247.
show abstract
Crizotinib is highly efficacious and more tolerable than chemotherapy for ALK+ non-small-cell lung cancer (NSCLC), but its progression-free survival benefit and intracranial efficacy have limitations. Head-to-head comparisons of next-generation ALK inhibitors in patients with ALK+ NSCLC progressing on crizotinib will contribute toward optimizing survival. This international, Phase III, randomized, open-label study (ALTA-3) will therefore assign patients with locally advanced or metastatic ALK+ NSCLC progressing on crizotinib to receive either brigatinib 180 mg qd (7-day lead-in at 90 mg qd) or alectinib 600 mg twice daily. The primary end point is progression-free survival as assessed by a blinded Independent Review Committee; the key secondary end point is overall survival. Clinical trial registration number: NCT03596866 (ClinicalTrials.gov)..
Begum, P.
Goldin, R.D.
Possamai, L.A.
Popat, S.
Severe Immune Checkpoint Inhibitor Hepatitis in KRAS G12C-Mutant NSCLC Potentially Triggered by Sotorasib: Case Report. Jto clinical and research reports,
Vol.2
(9),
pp. 100213-?.
show abstract
Sotorasib is a first-in-class small molecule that irreversibly inhibits KRAS G12C, locking it in an inactive state, inhibiting oncogenic signaling, and inducing a proinflammatory microenvironment. Here, we report the first case of life-threatening hepatitis in a patient with NSCLC shortly after commencing sotorasib, in which biopsy result was consistent with checkpoint inhibitor (CPI) immune-related adverse event, implicating sotorasib as being able to trigger CPI immune hepatitis. Given the large proportion of patients potentially treatable with sequential sotorasib after CPI, coupled with limited trial data, sotorasib-triggered CPI immune-related hepatitis should be considered in patients with sotorasib hepatotoxicity..
Hindocha, S.
Campbell, D.
Ahmed, M.
Giorgakoudi, K.
Sharma, B.
Yousaf, N.
Molyneaux, P.
Hunter, B.
Kalsi, H.
Cui, W.
Davidson, M.
Bhosle, J.
Minchom, A.
Locke, I.
McDonald, F.
O'Brien, M.
Popat, S.
Lee, R.W.
Immune Checkpoint Inhibitor and Radiotherapy-Related Pneumonitis: An Informatics Approach to Determine Real-World Incidence, Severity, Management, and Resource Implications. Frontiers in medicine,
Vol.8,
pp. 764563-?.
show abstract
Pneumonitis is a well-described, potentially life-threatening adverse effect of immune checkpoint inhibitors (ICI) and thoracic radiotherapy. It can require additional investigations, treatment, and interruption of cancer therapy. It is important for clinicians to have an awareness of its incidence and severity, however real-world data are lacking and do not always correlate with findings from clinical trials. Similarly, there is a dearth of information on cost impact of symptomatic pneumonitis. Informatics approaches are increasingly being applied to healthcare data for their ability to identify specific patient cohorts efficiently, at scale. We developed a Structured Query Language (SQL)-based informatics algorithm which we applied to CT report text to identify cases of ICI and radiotherapy pneumonitis between 1/1/2015 and 31/12/2020. Further data on severity, investigations, medical management were also acquired from the electronic health record. We identified 248 cases of pneumonitis attributable to ICI and/or radiotherapy, of which 139 were symptomatic with CTCAE severity grade 2 or more. The grade ≥2 ICI pneumonitis incidence in our cohort is 5.43%, greater than the all-grade 1.3-2.7% incidence reported in the literature. Time to onset of ICI pneumonitis was also longer in our cohort (mean 4.5 months, range 4 days-21 months), compared to the median 2.7 months (range 9 days-19.2 months) described in the literature. The estimated average healthcare cost of symptomatic pneumonitis is £3932.33 per patient. In this study we use an informatics approach to present new real-world data on the incidence, severity, management, and resource burden of ICI and radiotherapy pneumonitis. To our knowledge, this is the first study to look at real-world incidence and healthcare resource utilisation at the per-patient level in a UK cancer hospital. Improved management of pneumonitis may facilitate prompt continuation of cancer therapy, and improved outcomes for this not insubstantial cohort of patients..
Curcean, S.
Cheng, L.
Picchia, S.
Tunariu, N.
Collins, D.
Blackledge, M.
Popat, S.
O'Brien, M.
Minchom, A.
Leach, M.O.
Koh, D.-.
Early Response to Chemotherapy in Malignant Pleural Mesothelioma Evaluated Using Diffusion-Weighted Magnetic Resonance Imaging: Initial Observations. Jto clinical and research reports,
Vol.2
(12),
pp. 100253-?.
show abstract
Introduction We compared the magnetic resonance imaging total tumor volume (TTV) and median apparent diffusion coefficient (ADC) of malignant pleural mesothelioma (MPM) before and at 4 weeks after chemotherapy, to evaluate whether these are potential early markers of treatment response. Methods Diffusion-weighted magnetic resonance imaging was performed in 23 patients with MPM before and after 4 weeks of chemotherapy. The TTV was measured by semiautomatic segmentation (GrowCut) and transferred onto ADC maps to record the median ADC. Test-retest repeatability of TTV and ADC was evaluated in eight patients. TTV and median ADC changes were compared between responders and nonresponders, defined using modified Response Evaluation Criteria In Solid Tumors on computed tomography (CT) at 12 weeks after treatment. TTV and median ADC were also correlated with CT size measurement and disease survival. Results The test-retest 95% limits of agreement for TTV were -13.9% to 16.2% and for median ADC -1.2% to 3.3%. A significant increase in median ADC in responders was observed at 4 weeks after treatment ( p = 0.02). Correlation was found between CT tumor size change at 12 weeks and median ADC changes at 4 weeks post-treatment ( r = -0.560, p = 0.006). An increase in median ADC greater than 5.1% at 4 weeks has 100% sensitivity and 90% specificity for responders (area under the curve = 0.933, p < 0.001). There was also moderate correlation between median tumor ADC at baseline and overall survival ( r = 0.45, p = 0.03). Conclusions Diffusion-weighted magnetic resonance imaging measurements of TTV and median ADC in MPM have good measurement repeatability. Increase in ADC at 4 weeks post-treatment has the potential to be an early response biomarker..
Popat, S.
Hsia, T.-.
Hung, J.-.
Jung, H.A.
Shih, J.-.
Park, C.K.
Lee, S.H.
Okamoto, T.
Ahn, H.K.
Lee, Y.C.
Sato, Y.
Lee, S.S.
Mascaux, C.
Daoud, H.
Märten, A.
Miura, S.
Tyrosine Kinase Inhibitor Activity in Patients with NSCLC Harboring Uncommon EGFR Mutations: A Retrospective International Cohort Study (UpSwinG). The oncologist,
Vol.27
(4),
pp. 255-265.
show abstract
Background
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are standard of care for patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) with common mutations (Del19 or L858R); however, 7%-23% of NSCLC tumors harbor uncommon EGFR mutations. These mutations are highly heterogeneous, and developments in detection techniques are helping to identify mutations with little or no clinical data.
Patients and methods
In this retrospective, global, multi-center study (NCT04179890), existing health records were identified for consecutive EGFR TKI-naïve patients with uncommon EGFR mutations (T790M, ex20ins, major uncommon [G719X, L861Q, or S768I], or "other" mutations; compound mutations) treated with erlotinib, gefitinib, afatinib, or osimertinib in first or second line. Endpoints included time-to-treatment failure (TTF), objective response rate (ORR), and overall survival (OS).
Results
Overall, 246 patients (median age: 69.5 years; Asian: 84%) were included from 9 countries. Most patients (92%) received an EGFR TKI as first-line therapy; 54%, 43% and 3% received afatinib, first-generation TKIs, and osimertinib, respectively. Median TTF and OS with EGFR TKIs were 9.9 and 24.4 months; ORR was 43%. In patients treated with first-line chemotherapy (n = 20), median TTF and ORR were 6.6 months and 41%. Outcomes were most favorable in patients with major uncommon or compound mutations. Overall, TTF was 11.3 months with afatinib and 8.8 months with first-generation EGFR TKIs across mutation categories. In most mutation categories, median OS was >2 years.
Conclusion
In a real-world setting, EGFR TKIs were the preferred treatment option in patients with uncommon EGFR mutations; strongest outcomes were seen in patients with major uncommon and compound mutations..
Yang, J.C.
Schuler, M.
Popat, S.
Miura, S.
Park, K.
Passaro, A.
De Marinis, F.
Solca, F.
Märten, A.
Kim, E.S.
Afatinib for the Treatment of Non-Small Cell Lung Cancer Harboring Uncommon EGFR Mutations: An Updated Database of 1023 Cases Brief Report. Frontiers in oncology,
Vol.12.
show abstract
IntroductionPreviously, we developed a database of 693 patients with NSCLC and uncommon EGFR mutations treated with afatinib. Here, we provide an update of >1000 patients, with more data on specific mutations.MethodsPatients were identified from a prospective database developed by Boehringer Ingelheim and via literature review. Mutations were categorized as T790M-positive, exon 20 insertions, major uncommon (G719X, L861Q, S768I) and ‘others’. Patients with compound mutations (≥2 EGFR mutations) were analyzed separately. Key endpoints were time to treatment failure (TTF) and objective response rate (ORR).ResultsOf 1023 patients included, 587 patients were EGFR TKI-naïve and 425 were EGFR TKI-pretreated. The distribution of mutation categories was: major uncommon (41.4%); exon 20 insertions (22.3%); T790M (20.3%); and ‘others’ (15.9%); 38.6% had compound mutations. Overall, median TTF (TKI naïve/pretreated) was 10.7 and 4.5 months. ORR was 49.8% and 26.8%, respectively. In TKI-naïve patients, afatinib demonstrated activity against major uncommon mutations (median TTF: 12.6 months; ORR: 59.0%), ‘other’ mutations (median TTF: 10.7 months; ORR: 63.9%) including strong activity against E709X (11.4 months; 84.6%) and L747X (14.7 months; 80.0%), and compound mutations (11.5 months; 63.9%). Although sample sizes were small, notable activity was observed against specific exon 20 insertions at residues A763, M766, N771, and V769, and against osimertinib resistance mutations (G724S, L718X, C797S).ConclusionAfatinib should be considered as a first-line treatment option for NSCLC patients with major uncommon, compound, ‘other’ (including E709X and L747X) and some specific exon 20 insertion mutations. Moderate activity was seen against osimertinib resistance EGFR mutations..
Popat, S.
Liu, S.V.
Scheuer, N.
Gupta, A.
Hsu, G.G.
Ramagopalan, S.V.
Griesinger, F.
Subbiah, V.
Association Between Smoking History and Overall Survival in Patients Receiving Pembrolizumab for First-Line Treatment of Advanced Non–Small Cell Lung Cancer. Jama network open,
Vol.5
(5),
pp. e2214046-e2214046.
Aguilar‐Duran, S.
Mee, J.
Popat, S.
Heelan, K.
Atezolizumab‐induced linear
IgA
bullous dermatosis. British journal of dermatology,
.