Lynparza (olaparib) showed meaningful improvements in overall survival (OS) at six years for germline BRCA-mutated HER2-negative high-risk early breast cancer.- AstraZeneca + Merck Inc.

Updated results from the OlympiA Phase III trial showed AstraZeneca and MSD’s Lynparza (olaparib) demonstrated sustained, clinically meaningful improvements in overall survival (OS), invasive disease-free survival (IDFS) and distant disease-free survival (DDFS) at six years for patients with germline BRCA-mutated (gBRCAm) HER2-negative high-risk early breast cancer.

These results were presented at the San Antonio Breast Cancer Symposium 2024 (SABCS) (#GS1-09) and build on the positive primary results published in The New England Journal of Medicine.

At a median follow-up of 6.1 years in eligible patients, who had completed local treatment and standard neoadjuvant or adjuvant chemotherapy, results showed Lynparza reduced the risk of death by 28% (hazard ratio [HR] 0.72; 95% confidence interval [CI] 0.56-0.93) versus placebo. In addition, 87.5% of patients treated with Lynparza remained alive versus 83.2% of those on placebo.

Lynparza also demonstrated sustained and clinically meaningful improvements in the primary and secondary endpoints of IDFS and DDFS. Lynparza reduced the risk of invasive breast cancer recurrence, second cancers or death by 35% (HR 0.65; 95% CI; 0.53-0.78) and reduced the risk of distant disease recurrence or death by 35% (HR 0.65; 95% CI; 0.53-0.81) versus placebo. The benefit with Lynparza was consistent across all key subgroups, including patients with high-risk, hormone-receptor-positive disease.

Judy E. Garber, Chief of the Division of Cancer Genetics and Prevention at Dana-Farber Cancer Institute and co-principal investigator of the trial said: “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.”

The safety and tolerability profile of Lynparza in this trial was in line with that observed in prior clinical trials and no new safety signals were identified with longer follow-up. No evidence of an increased risk of myelodysplastic syndrome or acute myeloid leukaemia was observed compared to those on placebo.

The OlympiA 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 MSD.

OlympiA is a phase III, double-blind, parallel group, placebo-controlled, multicentre 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 primary endpoint of the trial is invasive disease-free survival defined as time from randomisation to date of first loco-regional or distant recurrence or new cancer or death from any cause. Key secondary endpoints include distant disease-free survival and overall survival, which is defined as time from randomisation until documented evidence of first distant recurrence of breast cancer or death without distant recurrence.