The trial of 100 patients – many of whom had inherited mutations to their BRCA genes – showed that niraparib had anti-tumour activity and was safe to move into larger, phase II trials.
Eight out of 20 ovarian cancer patients with BRCA mutations had a positive response to the drug, with tumours shrinking by at least 30 per cent. Two out of four patients with breast cancer and a BRCA mutation also showed a positive response to treatment, as did some patients with lung and prostate cancer.
The study is published in the journal Lancet Oncology and was led by researchers at The Institute of Cancer Research, London, working at The Royal Marsden NHS Foundation Trust.
Niraparib is one of a family of molecules called PARP inhibitors which are under development for the treatment of cancer. Others have shown promise as potential treatments, including one tested in a trial led by scientists at The Institute of Cancer Research (ICR) which announced early results last month.
PARP inhibitors target a protein in cancer cells called poly (ATP-ribose) polymerase, which helps repair wear and tear to DNA. They are particularly promising as a treatment for patients with mutations to genes called BRCA1 and BRCA2. In women, mutations to BRCA genes give a lifetime risk of developing breast cancer of up to 90 per cent. They are also linked with several other cancers in women and men.
In the study, doctors gradually increased patients’ dose of niraparib from a starting point of 30mg per day. They found that 300mg per day would give the best chance of targeting tumours in a larger trial, while keeping side-effects to a minimum.
Study leader Professor Johann de Bono, Professor of Experimental Cancer Medicine at the ICR and Honorary Consultant in Medical Oncology at The Royal Marsden, said: “PARP inhibitors hold a lot of promise as a potential treatment for several different types of cancer, and particularly cancers caused by mutations to BRCA genes. This study showed that a PARP inhibitor called niraparib is promising enough to move into a larger, phase II trial in patients with cancer.
“The idea of using PARP as a target in cancer therapy originally came from researchers here at the ICR, so it is particularly pleasing to see them showing success in early trials.”
The proteins produced by BRCA genes are responsible for repairing DNA. Without functioning copies of BRCA genes, healthy cells are likely to acquire more DNA mutations and become cancerous. However, cancer cells with mutated BRCA genes become overly reliant on the PARP system of DNA repair to survive. PARP inhibitors exploit this weakness in BRCA positive cancers: without either the PARP or BRCA systems of DNA repair working properly, too many DNA breaks in cancer cells build up, causing them to die.