OlympiA: A randomized phase III trial of olaparib as adjuvant therapy in patients with high-risk HER2-negative breast cancer (BC) and a germline BRCA1/2 mutation (gBRCAm)

Abstract

Background: In a Phase II study (NCT00494234), treatment with olaparib, a potent, orally available PARP inhibitor, exerted antitumor activity in patients (pts) with advanced BC harboring a gBRCAm. In a randomized phase III trial, olaparib significantly improved PFS compared to chemotherapy (CT) for patients with HER2- negative gBRCAm advanced BC (OlympiAD, NCT02000622, ASCO 2017). OlympiA (NCT02032823) is a phase III trial of olaparib as adjuvant therapy for pts with high risk gBRCAm HER2-negative BC who have completed local treatment and (neo)-adjuvant CT. Trial design: OlympiA is a double-blind trial in which high risk HER2-negative pts are randomized (1:1) to receive treatment with olaparib (300 mg tablets bid [2 x 150 mg]) or placebo for 12 months. Eligible pts must have completed local treatment and at least 6 cycles of (neo)-adjuvant containing anthracyclines and/or taxanes. Pts with triple negative BC (TNBC) must have ≥pT2 or ≥pN1 in the adjuvant and non-pCR in the neoadjuvant setting. Pts with hormone receptor (HR) positive BC must have≥4 positive lymph nodes in the adjuvant and non-pCR and CPS&EG score≥3 in the neoadjuvant setting. Pts must also harbor a deleterious gBRCAm. Stratification factors include hormone receptor status, prior neoadjuvant versus adjuvant CT, and whether pts have received platinum therapy for current BC. The primary objective is invasive diseasefree survival (IDFS). Efficacy assessments will be made by mammograms/breast MRI scans annually for 10 years, beginning 6 months from randomization, and by medical history/physical examination from randomization every 3 months for 2 years, then every 6 months for a further 3 years and annually thereafter. Secondary objectives include overall survival, distant DFS, incidence of new non-BCs, HRQoL, safety and tolerability. The primary IDFS analysis will be performed after 330 IDFS events using a stratified log-rank test. Patient enrolment began in April 2014 and is currently ongoing. The target number for randomization is 1500 patients across ∼500 sites and∼25 countries worldwide.