AstraZeneca in collaboration with Merck—recognized as MSD outside the US and Canada—has unveiled enduring data from the OlympiA phase 3 trial, demonstrating that Lynparza (olaparib) achieves long-lasting, meaningful clinical improvements in overall survival (OS), invasive disease-free survival (IDFS), and distant disease-free survival (DDFS) for individuals with germline BRCA-mutated (gBRCAm), HER2-negative, high-risk early breast cancer.
These findings were disclosed at the 2024 San Antonio Breast Cancer Symposium (#GS1-09) and align with the positive initial outcomes previously detailed in The New England Journal of Medicine.
Judy E. Garber, a key clinical leader at the Dana-Farber Cancer Institute and co-primary investigator of the study, expressed, “The comprehensive long-range data from OlympiA reinforce the continued clinical advantage of a one-year olaparib adjuvant therapy for patients with gBRCA mutated high-risk HER2-negative early breast cancer, even after a six-year period, with the sustained benefit across all patient categories, coupled with positive toxicity and reproductive data for this typically younger demographic. These findings underscore the critical need for germline BRCA testing during diagnosis, ensuring timely identification of eligible patients who could benefit from early intervention with olaparib.”
Globally, breast cancer ranks as the second most prevalent cancer, with estimates of 2.3 million new cases in 2022. Approximately 63% of breast cancer diagnoses occur at the early stage, with BRCA mutations present in 5-10% of cases.
Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, commented: “Two years ago, Lynparza emerged as the pioneering PARP inhibitor demonstrating survival benefits in gBRCA-mutated, HER2-negative, high-risk early-stage breast cancer. Observing this advantage persist six years after follow-up is a major triumph for patients and exemplifies how Lynparza is reshaping the treatment landscape for BRCA-mutated early-stage breast cancer.”
Dr. Eliav Barr, Senior Vice President, overseeing global clinical development and chief medical officer at Merck Research Laboratories, noted: “The prolonged and stable efficacy seen with the OlympiA trial substantiates Lynparza as a vital treatment choice for those facing the arduous challenge of this aggressive breast cancer variant.”
After a median follow-up period of 6.1 years (with a maximum of 9.6 years), among qualified patients who finalized local therapy alongside standard neoadjuvant or adjuvant chemotherapy, Lynparza reduced mortality risk by 28% (HR 0.72; 95% CI 0.56-0.93) compared to placebo. Furthermore, 87.5% of Lynparza recipients were alive in contrast to 83.2% on placebo.
Lynparza continued to show meaningful, consistent benefits across primary and secondary metrics, such as IDFS and DDFS. The recurrence risk reduction for invasive breast cancer, secondary cancer, or death was 35% (HR 0.65; 95% CI; 0.53-0.78), with a similar 35% risk reduction (HR 0.65; 95% CI; 0.53-0.81) in distant disease recurrence or death, compared to placebo—all key demographic groups echoed these benefits, including patients with high-risk, hormone-receptor-positive disease.
The safety profile of Lynparza, congruent with earlier trials, revealed no new safety issues relating to prolonged observation. Significantly, there was no increased risk of myelodysplastic syndrome or acute myeloid leukemia relative to the placebo group.
Coordinated by the Breast International Group (BIG) with partners including NRG Oncology and the US National Cancer Institute (NCI), among others, the OlympiA trial underpins these findings.
Lynparza achieves regulatory approval across various regions, including the US, EU, Japan, and beyond for treating gBRCAm, HER2-negative high-risk early breast cancer based on OlympiA’s outcomes. Approval also extends to managing gBRCAm, HER2-negative metastatic breast cancer, covering locally advanced cases in the EU.
OlympiA is a comprehensive, phase III, double-blind, multicenter trial; it’s designed to evaluate Lynparza’s impact in comparison to placebo as a 12-month adjuvant therapy for adults with gBRCAm HER2-negative early-stage breast cancer, post-neoadjuvant or adjuvant chemotherapy. Central endpoints include invasive disease-free survival—the timeframe to recurrence, new cancer, or mortality—and key secondary endpoints such as distant disease-free survival and overall survival.
The BRCA 1 and 2 genes are pivotal for DNA repair and genetic cell stability. When these genes mutate, the resulting protein malfunctions, leading to improper DNA repair and potential genetic cell instability, increasing cancer likelihood.
Early stage breast cancer is localized or involves regional lymph nodes, absent of distant spread. The US sees a 99.6% 5-year survival rate for localized breast cancer, dipping to 86.7% when regional spread is noted. Despite early treatment advances, up to 30% of those with high-risk features face early recurrence, compounded by gBRCA-linked diagnoses at younger ages relative to non-mutation cases.
Since July 2017, AstraZeneca and Merck have partnered globally on oncology developments, focusing on Lynparza among others as monotherapies or in combination treatments, integrating new cancer medicines without overlapping PD-L1 or PD-1 developments.
Merck’s mission centers on transforming advanced cancer treatment through innovative oncology solutions and fostering accessibility. The focus extends to immuno-oncology, one of our industry’s largest development programs, and strengthening our portfolio through acquisitions ensuring ongoing advancements in combating advanced cancers.