A phase 3 double-blind, randomized clinical trial published on The New England Journal of Medicine showed that adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than placebo, among patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants.
In the OlympiA trial, authors hypothesized that the PARP inhibitor olaparib would provide benefit as an adjuvant therapy for patients with germline BRCA1 or BRCA2 pathogenic or likely pathogenic variant–associated early breast cancer who have a high risk of recurrence despite standard-of-care local and systemic therapy. The trial involved 1836 patients in 420 centers across 23 countries; they had HER2-negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors; they had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned to 1 year of oral olaparib, or placebo; the primary end point was invasive disease–free survival. The 3-year invasive disease– free survival was 85.9% in the olaparib group and 77.1% in the placebo group, whereas the 3-year distant disease–free survival was 87.5% and 80.4% respectively; olaparib was associated with fewer deaths than placebo but had limited effects on global patient-reported quality of life. Its safety data were consistent with known side effects of olaparib, with no excess serious adverse events or adverse events of special interest. «The OlympiA trial showed that 1 year of adjuvant olaparib can meaningfully reduce recurrence risk and prevent progression to metastatic disease among patients with high-risk early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, with high adherence rates and primarily a low-grade toxicity profile. The trial provides evidence that germline BRCA1 and BRCA2 sequencing is an important biomarker for the selection of systemic therapy in early breast cancer», authors conclude.