Image: Breast cancer cells. Credit: Anne Weston, Francis Crick Institute. CC BY-NC 4.0.
The targeted drug olaparib improves survival in women with high-risk, early-stage breast cancer who have inherited faults in their BRCA1 or BRCA2 genes, new results from a major clinical trial show.
New findings from the phase III OlympiA trial, presented at the ESMO Virtual Plenary 2022, show that olaparib added to standard treatment cuts the risk of women dying by 32 per cent – resulting in more women remaining cancer free and becoming breast cancer survivors.
Professor Andrew Tutt at the ICR and King’s College London was Chair of the Steering Committee for the study, and was also involved in early laboratory research on PARP inhibitors such as olaparib, and their subsequent clinical development. The Breast International Group (BIG) coordinated the international OlympiA study, involving 671 study locations, globally across multiple partners.
OlympiA trial researchers studied 1,836 women with HER-2 negative breast cancer, who also had a mutation in their BRCA1 or BRCA2 genes and had undergone standard treatment, including surgery, chemotherapy, hormonal therapies and radiotherapy, where appropriate. Patients were randomly allocated to receive either 300mg twice day of olaparib or a placebo for one year and were then followed up.
The trial will follow participants for a total of 10 years but reported its first results after just two and a half years following a planned review by an independent monitoring committee which found that olaparib reduced the risk of breast cancer returning by 42 per cent.
BIG coordinated the trial’s UK sites through the Clinical Trials and Statistics Unit at the ICR.
Targeting specific biology of BRCA1 and BRCA2
Olaparib targets the specific biology of the BRCA genes, killing cancer cells while leaving healthy cells alone. The ICR worked with many partners including Breast Cancer Now and Cancer Research UK to discover how to use olaparib and other PARP inhibitor drugs for patients with mutations in their BRCA1 or BRCA2 genes, or faults in other DNA repair genes.
This research paved the way for many clinical trials with international partners which have led to the development of olaparib as a treatment for some patients with advanced ovarian, breast, prostate and pancreatic cancer.
Individualised and targeted treatment
OlympiA steering committee chair Professor Andrew Tutt, Professor of Oncology at The Institute of Cancer Research, London, and King’s College London said:
“Today’s results are great news for many women with inherited breast cancer. Most breast cancers are identified in the early stages and many patients will do very well, but for some, the risk of cancer returning remains unacceptably high, even after chemotherapy.
“OlympiA has shown that after selecting women with inherited BRCA mutations through genetic testing, we can use olaparib to directly target the weakness in their cancer and improve their survival. I hope to see BRCA1 and BRCA2 testing used for more women diagnosed with early-stage breast cancer, so that we can determine who can benefit from this personalised treatment approach. Olaparib provides a much needed new individualised and targeted treatment option to keep more women with inherited breast cancer free of disease and alive and well after their initial treatment.”
A major step forward
Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, London, said:
“This is a major step forward in treatment of early-stage inherited breast cancer. Olaparib has major benefits for this group of patients, increasing their chances of remaining cancer free and potentially being cured after initial treatment. We hope olaparib will now be licensed in Europe and approved in the UK for NHS patients without delay.
“Olaparib was the first cancer drug in the world to directly target inherited genetic faults following landmark research by scientists at the ICR. The story of olaparib shows how a fundamental scientific discovery, which identified one of cancer's weaknesses, can lead to game-changing new treatments. It is also a great UK success story, and I am proud of the pivotal role the ICR’s scientists played in its development.”
OlympiA is a collaborative study being coordinated worldwide by BIG in partnership with NRG Oncology, the US National Cancer Institute (NCI), Frontier Science & Technology Research Foundation (involving research staff in the US and in the affiliate office in Scotland), AstraZeneca and MSD. The trial is sponsored by NRG Oncology in the US and by AstraZeneca outside the US.
Patients on the trial will continue to be followed up for a total of 10 years.
Olaparib was developed as a genetically targeted cancer treatment following landmark research in 2005 by ICR scientists. Read more about how olaparib was developed.
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