A major new trial presented today at the American Society for Clinical Oncology (ASCO) Conference in Chicago has shown that breast cancer drug olaparib (Lynparza) can give women living with BRCA-mutated incurable breast cancer significant extra time before their disease progresses, compared to standard chemotherapy.
The OlympiAD (phase III) trial, led by Mark Robson MD at the Memorial Sloan Kettering Cancer Center in New York and funded by AstraZeneca, tested olaparib versus chemotherapy for patients with HER2-negative BRCA-mutation advanced breast cancer. It found that olaparib delayed progression by an average of around 3 months, compared to chemotherapy (7.0 months vs 4.2 months respectively).
Olaparib – which is one of a new class of drugs known as PARP inhibitors – was first developed as a cancer treatment following landmark research by UK scientists at the Breast Cancer Now Research Centre at the Institute of Cancer Research, London in 20051, who demonstrated for the first time that cancer cells with BRCA1 and BRCA2 mutations were very sensitive to PARP inhibitors.
Olaparib works by blocking a DNA repair protein known as PARP, which can help BRCA-mutated cancer cells survive despite their main DNA repair kits (BRCA1 or BRCA2) not functioning properly. By blocking PARP with olaparib, breast cancer cells which have BRCA mutations can be rendered unable to repair their DNA – causing them to die.
Baroness Delyth Morgan, Chief Executive at Breast Cancer Now, said:
“This outstanding news represents a significant step forward in the treatment of BRCA-mutant secondary breast cancer.
“Olaparib could now become the first biologically targeted drug for a group of patients with incurable and aggressive breast cancer who currently have few treatment options. That it can offer around three extra months before the disease progresses compared to chemotherapy – and a better quality of life during that time – will be invaluable to so many women and their families.
“It also represents an extraordinary achievement for UK science, with PARP inhibitors first being developed as a cancer treatment following research at the Breast Cancer Now Research Centre at the Institute of Cancer Research, London in 2005.
“But our work in optimising PARP inhibitors for use in the clinic is not yet done, and research is ongoing to uncover how we can best identify who will benefit most from them. These drugs are already being used to treat ovarian cancer patients who carry BRCA mutations and we very much hope that breast cancer patients will now be able to benefit from them in the near future.”
Professor Andrew Tutt, Director of the Breast Cancer Now Research Centre at The Institute of Cancer Research, London, said:
“It is fantastic news that olaparib delays the progression of advanced breast cancer in women who have inherited BRCA1 or BRCA2 mutations – the most common type of inherited breast cancer.
“Olaparib is already available for women with BRCA-mutant advanced ovarian cancer, and is the first drug to be approved that is directed against an inherited genetic mutation. It is a perfect example of how understanding a patient’s genetics and the biology of their tumour can be used to target its weaknesses and personalise treatment.
“We are getting much better at curing patients with breast cancer that is diagnosed early – but once the disease has spread around the body, it is much more difficult to treat. We need to see more innovative new cancer drugs like olaparib being developed, to give these women a better quality of life for longer.”
1 Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy – Hannah Farmer, Nuala McCabe, Christopher J. Lord, Andrew N. J. Tutt, Damian A. Johnson, Tobias B. Richardson, Manuela Santarosa, Krystyna J. Dillon, Ian Hickson, Charlotte Knights, Niall M. B. Martin, Stephen P. Jackson, Graeme C. M. Smith and Alan Ashworth
Read our blog on Breast Cancer Now's involvement in the discovery of PARP inhibitors