Updated results from the OlympiA Phase III trial demonstrate that Lynparza (olaparib), developed by AstraZeneca and Merck, provides a sustained and clinically meaningful overall survival (OS) benefit for patients with germline BRCA-mutated (gBRCAm), HER2-negative high-risk early breast cancer. The findings, presented at the San Antonio Breast Cancer Symposium 2024, build upon initial positive results published in The New England Journal of Medicine.
Significant Survival Improvements
After a median follow-up of 6.1 years, Lynparza reduced the risk of death by 28% compared to placebo (HR 0.72; 95% CI 0.56-0.93). Specifically, 87.5% of patients treated with Lynparza were alive compared to 83.2% on placebo. These results underscore the potential of Lynparza to transform the treatment landscape for this aggressive form of breast cancer.
Impact on Disease Recurrence
Lynparza also demonstrated significant improvements in both invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The risk of invasive breast cancer recurrence, second cancers, or death was reduced by 35% (HR 0.65; 95% CI 0.53-0.78). Similarly, the risk of distant disease recurrence or death was also reduced by 35% (HR 0.65; 95% CI 0.53-0.81). The benefits were consistent across all key subgroups, including patients with high-risk, hormone-receptor-positive disease.
Expert Commentary
Judy E. Garber, Chief of the Division of Cancer Genetics and Prevention at Dana-Farber Cancer Institute and co-principal investigator of the trial, emphasized the importance of these findings: “These exciting long-term data from OlympiA confirm that adjuvant treatment with olaparib for one year continues to deliver clinically meaningful survival benefit for patients with germline BRCA-mutated high-risk HER2-negative early breast cancer even after six years, with benefit persisting in all subgroups and with toxicity and pregnancy data reassuring for this generally younger group. These data reinforce the importance of germline BRCA testing at the time of diagnosis, so we can identify all eligible patients who may benefit from treatment with olaparib as early as possible.”
Safety and Tolerability
The safety and tolerability profile of Lynparza in the OlympiA trial remained consistent with previous clinical trials. No new safety signals were identified with longer follow-up, and there was no evidence of an increased risk of myelodysplastic syndrome or acute myeloid leukemia compared to placebo.
About the OlympiA Trial
The OlympiA trial is a Phase III, double-blind, placebo-controlled, multicenter trial evaluating the efficacy and safety of Lynparza tablets versus placebo as a 12-month adjuvant treatment for adult patients with gBRCAm HER2-negative early breast cancer who have completed neoadjuvant or adjuvant chemotherapy. The trial is coordinated by the Breast International Group (BIG) in partnership with NRG Oncology, the US National Cancer Institute (NCI), the Frontier Science & Technology Research Foundation (FSTRF), AstraZeneca, and Merck.
Current Approvals and Future Directions
Lynparza is currently approved in the US, EU, Japan, and other countries for the treatment of gBRCAm, HER2-negative high-risk early breast cancer, as well as for gBRCAm, HER2-negative metastatic breast cancer. These long-term results from the OlympiA trial further solidify Lynparza's role as a critical treatment option for patients with BRCA-mutated early-stage breast cancer.
