One year of adjuvant treatment with olaparib (Lynparza) continues to demonstrate long-term survival benefits for women with high-risk, early-stage, HER2-negative breast cancer who also have BRCA1 or BRCA2 mutations. New findings from the phase III OlympiA trial, presented at the San Antonio Breast Cancer Symposium (SABCS) 2024, show that olaparib significantly reduces the risk of cancer recurrence and death.
OlympiA Trial Details
The OlympiA trial, coordinated by the Breast International Group (BIG), involved 1,836 women with HER2-negative breast cancer and BRCA1/2 mutations who had already undergone standard treatment, including surgery and chemotherapy. Participants were randomized to receive either 300mg of olaparib twice daily or a placebo for one year.
Key Findings
At a median follow-up of 6.1 years, the results showed:
- A 35% reduction in the risk of cancer recurrence (HR 0.65; 95% CI; 0.53-0.78).
- A 28% reduction in the risk of death (HR 0.72; 95% confidence interval [CI] 0.56-0.93).
- After six years, 87.5% of patients treated with olaparib were alive, compared to 83.2% in the placebo group.
Professor Andrew Tutt from The Institute of Cancer Research, London, and King’s College London, the global lead investigator for the OlympiA study, emphasized the importance of genetic testing: “The OlympiA trial has shown the importance of genetic testing for women diagnosed with early-stage breast cancer, to identify cancers with BRCA1 and BRCA2 mutations so that we can determine who can benefit from this personalised treatment approach.”
The study also reported that the safety and tolerability profile of olaparib was consistent with previous clinical trials, with no new safety signals identified. There was no evidence of an increased risk of myelodysplastic syndrome or acute myeloid leukemia compared to placebo.
Clinical Significance
Inherited mutations in BRCA1 and BRCA2 genes account for approximately 5% of all breast cancers. Women with these mutations are often diagnosed at a younger age and may require more intensive treatment. Olaparib, a PARP inhibitor, targets the specific biology of these BRCA-mutated cancer cells, killing them while sparing healthy cells.
Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, London, highlighted the impact of these findings: “The results from the OlympiA trial continue to provide hope and reassurance to women with early-stage, high-risk breast cancer. Olaparib has major benefits for this group of patients, increasing their chances of remaining cancer free in the long-term and potentially being cured after initial treatment.”
Regulatory Implications
Earlier results from the OlympiA trial have already led to recommendations by NICE (National Institute for Health and Care Excellence) to grant access to olaparib for people in England and Wales with early-stage, high-risk breast cancer and inherited BRCA1 or BRCA2 mutations following standard treatment.
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, noted, “To see this benefit continue at six years of follow-up is tremendous for patients and reinforces how olaparib is continuing to transform the treatment of BRCA - mutated early-stage breast cancer.”
