A first interim analysis of the OlympiA trial demonstrates significantly improved invasive disease-free survival in patients with high risk, HER2-negative, germline BRCA1/2-mutated primary breast cancer after 1 year of adjuvant treatment with the PARP inhibitor olaparib.
Despite (neo)adjuvant chemotherapy, recurrence rates in patients with early breast cancer with BRCA1/2 germline mutation (gBRCAm) can be high. Novel adjuvant treatments are needed. The OlympiA trial (NCT02032823) explores the efficacy and safety of adjuvant treatment with olaparib in patients with gBRCAm, high-risk, HER2-negative primary breast cancer. The study enrolled 1,836 patients with gBRCAm and HER2-negative (triple-negative or hormone-receptor-positive), high-risk, early breast cancer after primary local treatment and adjuvant (49.9%) or neoadjuvant (50.1%) chemotherapy. Patients were randomised 1:1 to 1 year of continuous oral olaparib (300 mg BID) or placebo for 1 year. Endocrine therapy and bisphosphonates were allowed.
The primary endpoint was invasive disease-free survival in the intention-to-treat population. Secondary endpoints included distant disease-free survival, overall survival, and safety. Prof. Andrew Tutt (Institute of Cancer Research, UK) presented the first interim analysis of OlympiA . At 2.5 years median follow-up, results showed a significant benefit of olaparib versus placebo regarding invasive disease-free survival (HR 0.58; P<0.0001).
Three-year invasive disease-free survival was 85.9% versus 77.1% (absolute difference 8.8%). Distant disease-free survival was also significantly improved with olaparib (HR 0.57; P<0.0001). Three-year distant disease-free survival was 87.5% versus 80.4% (absolute difference 7.1%). Overall survival was greater for olaparib than placebo but was not statistically significant at the time of the interim analysis. Three-year overall survival was 92.0% versus 88.3% (absolute difference 3.7%).
No unexpected adverse events of olaparib were observed. Global Health Quality of Life Score was not significantly affected by treatment with olaparib nor in patients treated with olaparib after adjuvant chemotherapy of in patients treated with olaparib after neoadjuvant chemotherapy. Based on these interim-results, Prof. Tutt concluded that “patients with high-risk, HER2-negative, early breast cancer and germline BRCA1/2 mutations benefit from adjuvant olaparib for 1 year after completion of adjuvant or neoadjuvant chemotherapy.”
1. Tutt A, et al. OlympiA: A phase III, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)adjuvant chemotherapy in patients with germline BRCA1/2 mutations and high-risk HER2-negative early breast cancer. ASCO 2021 Virtual Meeting, abstract LBA1.