PROpel: Efficacy of abiraterone + olaparib vs. abiraterone + placebo in the first-line treatment of patients with asymptomatic/mildly symptomatic metastatic castration-resistant prostate cancer (mCRPC) at baseline

Introduction & Objectives: The Phase III PROpel trial enrolled patients (pts) with mCRPC and either asymptomatic/mildly symptomatic or symptomatic disease, thereby accommodating diverse indications for first‐line abiraterone (abi) globally and reflecting real‐world clinical practice after the approval of abi in 2012. For pts who were asymptomatic/mildly symptomatic, we report exploratory efficacy analyses of radiographic progression‐free survival (rPFS) from the primary data cut‐off (DCO1: 30/07/21), time to second progression or death (PFS2) and overall survival (OS) from a later data cut‐off (DCO2: 14/03/22). Materials & Methods: Pts were randomised 1:1 to olaparib (ola; 300 mg twice daily [bid]) or placebo (pbo) + abi (1000 mg once daily) and prednisone/prednisolone (5 mg bid) irrespective of homologous recombination repair mutation (HRRm) status. Pts with a Brief Pain Inventory ‐ Short Form (BPI‐SF) item 3 score of <4 and no opiate use at baseline were classed as asymptomatic/mildly symptomatic. Time‐to‐event analyses were performed by a Cox proportional hazards model and an rPFS sensitivity analysis by blinded independent central review (BICR). Results: 560 of 796 randomised pts were classed as asymptomatic/mildly symptomatic (abi+ola, n=266; abi+pbo, n=294). Median rPFS per investigator assessment in asymptomatic/mildly symptomatic patients (DCO1) was 27.6 months for abi+ola vs 19.1 months for abi+pbo (HR 0.59; 95% CI 0.46–0.76; Figure); median rPFS by BICR (DCO1) was 27.6 vs 17.5 months, respectively (HR 0.58; 95% CI 0.45–0.75). At DCO2, 43 (16%) pts treated with abi+ola had PFS2 events vs 72 (25%) pts treated with abi+pbo (HR 0.60; 95% CI 0.41–0.87); median PFS2 was not reached ineither arm. 77 (29%) OS events were reported for abi+ola vs 111 (38%) for abi+pbo (HR 0.73; 95% CI 0.54–0.97); median OS was not reached in either arm. [Figure presented] Conclusions: At primary analysis, PROpel met its primary endpoint of significantly prolonged rPFS with abi+ola vs abi+pbo in first‐line mCRPC irrespective of HRRm status. Exploratory analyses demonstrated that abi+ola also provided clinically meaningful efficacy benefits in asymptomatic/mildly symptomatic pts, including a median rPFS value that reached 27.6 months.