Adjuvant olaparib in the subset of patients from Japan with BRCA1- or BRCA2-mutated high-risk early breast cancer from the phase 3 OlympiA trial

Background The efficacy and safety of olaparib compared with placebo in the subset of patients from Japan in the phase 3 OlympiA trial (NCT02032823) are reported here and contextualized with reference to the global OlympiA population. Methods Patients with germline BRCA1 and/or BRCA2 pathogenic variants and HER2-negative, high-risk early breast cancer who had received neoadjuvant or adjuvant chemotherapy and completed local treatment were eligible. Patients were randomized 1:1 to receive olaparib or placebo for 1 year. Primary endpoint: invasive disease-free survival (IDFS). Secondary endpoints: distant disease-free survival (DDFS), overall survival (OS), and safety. Data are reported from the first pre-specified interim analysis (data cut-off [DCO] March 27, 2020) and the second, event driven, pre-specified interim analysis of OS (DCO July 12, 2021) in patients from Japan. Results 140 patients were randomized in Japan (olaparib, n = 64; placebo, n = 76). At the first pre-specified interim analysis (median follow-up: 2.9 years), hazard ratios (HRs) for adjuvant olaparib compared with placebo were 0.5 for IDFS (95% confidence interval [CI] 0.18–1.24) and 0.41 for DDFS (95% CI 0.11–1.16). At the second pre-specified interim analysis of OS, three deaths occurred in the olaparib group versus six deaths in the placebo group (HR, 0.62 [95% CI 0.13–2.36]). Findings were consistent with those for the global population. No new safety signals were observed. Conclusions While this analysis in a Japanese subset of patients was not powered to detect population-related treatment differences, efficacy and safety analysis results were consistent with the global OlympiA population, suggesting the findings from the global study are generalizable to clinical practice in Japan.