Tuesday 4 June 2013
A new potential cancer drug designed to be effective in tumours with faulty BRCA genes has generated impressive responses in an early-stage clinical trial.
The potential drug, called BMN 673, targets DNA repair in cancer cells, and is designed specifically to attack tumours that have been left vulnerable by genetic mutations.
A small study found the drug was well tolerated by patients and showed ‘excellent anti-tumour activity’, a researcher from The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust announced.
The trial results were presented at the American Society of Clinical Oncology (ASCO) meeting in Chicago, US, late yesterday. The trial was funded by US firm BioMarin Pharmaceutical and also involved the University of Newcastle and several institutions in the US (1).
The trial results covered 70 patients with a range of cancers – including ovarian or peritoneal, and breast. Patients with cancers linked to BRCA mutations saw the most substantial improvement.
The researchers used different measures of the drug’s effect on tumour instability and breakdown. One was a clinical score called RECIST, which includes a range of measures such as whether visible lesions, or cracks, appear in the walls of tumours after treatment. Some 11 of 25 evaluable ovarian cancer patients with BRCA mutations had a RECIST-positive response to treatment, as did seven of 18 breast cancer patients with BRCA mutations. Signs of some clinical benefit were seen in several more patients (2).
BRCA mutations reduce cells’ ability to repair their DNA, and when inherited substantially increase the risk of developing a range of cancers, including breast, ovarian and prostate.
No targeted treatments have yet been approved specifically for use in patients who have inherited BRCA mutations.
BMN 673 – which is yet to be given a trade name – is one of a handful of a family of molecules called PARP inhibitors which are under development for the treatment of cancer. BMN 673 is one of the most promising PARP inhibitors currently being tested in clinical trials.
Study researcher Professor Johann de Bono, Professor of Experimental Cancer Medicine at The Institute of Cancer Research, London, and Honorary Consultant in Medical Oncology at The Royal Marsden, said: "Patients with germline BRCA-associated tumours have no targeted treatment options, and there is a real need for these to be developed. Our promising study showed that BMN 673, a potent member of a family of potential drugs called PARP inhibitors, had excellent anti-tumour activity. It’s one of a range of new-style cancer therapies that target specific molecular defects in tumours and offer the potential of more personalised treatments to patients, including those with BRCA mutations.”
Researchers now plan a larger clinical trial of BMN 673 to further explore its potential effectiveness.
Notes to editors
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PARP, a protein called poly ADP ribose polymerase, helps repair mistakes in DNA that occur naturally when a cell divides to form new cells. PARP inhibitors are particularly promising in cancers linked with BRCA mutations because the tumours are overly reliant on the PARP system for essential DNA repair.
Professor Alan Ashworth, Chief Executive of The Institute of Cancer Research, was among those to propose that PARP inhibition could offer an effective treatment in patients carrying BRCA mutations.
- The collaborating institutions in the research were: The Institute of Cancer Research, London; The Royal Marsden NHS Foundation Trust, London; Indiana University, Indianapolis; Northern Institute for Cancer Research, Newcastle University, Newcastle Upon Tyne; BioMarin Pharmaceutical, Novato; Virginia G. Piper Cancer Center at Scottsdale Healthcare/TGen, Scottsdale; Virginia G. Piper Cancer Center at Scottsdale Healthcare, Scottsdale; Indiana University School of Medicine, Indianapolis; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles; The University of Texas MD Anderson Cancer Center, Houston; University of Michigan, Ann Arbor Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare/TGen, Scottsdale.
- In the 28 ovarian cancer patients with BRCA mutations, the RECIST response rate was 44% or 11 of 25 evaluable patients, the CA-125 response rate was 70% or 19 of 27 evaluable patients and the clinical benefit response rate was 82% or 23 of 28 patients.
In the 18 germline BRCA breast cancer patients, the RECIST response rate was 39% or seven of 18 patients and the clinical benefit rate was 67% or 12 of 18 patients. Of the 18 germline BRCA breast cancer patients, there were six partial responses (three yet to be confirmed) and one complete response. Four ongoing patients have had stable disease for less than 12 weeks. Treatment is ongoing in 12 of the 18 breast cancer patients in the study.
The Institute of Cancer Research, London, is one of the world’s most influential cancer research institutes.
Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients’ lives. Through its unique partnership with The Royal Marsden Hospital and ‘bench-to-bedside’ approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four cancer centres globally.
The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it leads the world at isolating cancer-related genes and discovering new targeted drugs for personalised cancer treatment.
As a college of the University of London, the ICR provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public.
The ICR’s mission is to make the discoveries that defeat cancer. For more information visit www.icr.ac.uk
The Royal Marsden NHS Foundation Trust
The Royal Marsden opened its doors in 1851 as the world’s first hospital dedicated to cancer diagnosis, treatment, research and education.
Today, together with its academic partner, The Institute of Cancer Research (ICR), it is the largest and most comprehensive cancer centre in Europe treating over 44,000 patients every year. It is a centre of excellence with an international reputation for groundbreaking research and pioneering the very latest in cancer treatments and technologies. The Royal Marsden also provides community services in the London boroughs of Sutton and Merton and in June 2010, along with the ICR, the Trust launched a new academic partnership with Mount Vernon Cancer Centre in Middlesex.
Since 2004, the hospital’s charity, The Royal Marsden Cancer Charity, has helped raise over £50 million to build theatres, diagnostic centres, and drug development units.
Prince William became President of The Royal Marsden in 2007, following a long royal connection with the hospital.
For more information, visit www.royalmarsden.nhs.uk