Multinational phase 3 trial of adjuvant olaparib for germline BRCA1/2-associated HER2-negative early breast cancer: update from OlympiA

The multinational randomized phase 3 OlympiA trial compared 1 year of adjuvant olaparib to placebo in 1836 patients with pathogenic or likely pathogenic BRCA1/2 germline variants (gBRCApv) and high-risk HER2-negative early breast cancer. Previous interim analyses showed statistically significant improvements in outcomes with olaparib irrespective of hormone receptor status, prior platinum, timing of prior chemotherapy, or type of gBRCApv. Results of the third prespecified interim analysis, with a median follow-up of 6.1 years, have now been published. Primary endpoint was invasive disease-free survival (IDFS); secondary endpoints were distant disease-free survival (DDFS) and overall survival (OS). Olaparib benefits were maintained in IDFS (HR 0.65; 95% CI 0.53-0.78), DDFS (0.65; 0.73-0.81), and OS (0.72; 0.56-0.93). The 6-year OS rate for olaparib versus placebo was 87.5% versus 83.2% (difference 4.4%; 95% CI 0.9-6.7). Olaparib benefit was consistent across all key subgroups. With olaparib versus placebo, there were fewer BRCA-associated new breast and ovarian/fallopian tube cancers, and no increase in adverse events of special interest, such as MDS/AML. The authors conclude that at 6.1 years median follow-up, 1 year of adjuvant olaparib after (neo)adjuvant chemotherapy demonstrates ongoing clinically meaningful improvements in outcomes of patients with gBRCApv and high-risk, HER2-negative early breast cancer, with acceptable toxicity and without increased risk of MDS/AML.