Patient-reported Outcomes for Men with Metastatic Castration-resistant Prostate Cancer Who Received Olaparib plus Abiraterone Versus Placebo plus Abiraterone in the Phase 3 PROpel Study

Abstract

Background and objective: The phase 3 PROpel study showed a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) with olaparib + abiraterone versus placebo + abiraterone in the first-line setting for patients with metastatic castration-resistant prostate cancer (mCRPC) unselected by mutation status for homologous recombination repair genes. Here we report patient-reported outcomes and results for other symptom-related endpoints.

Methods: Patients were randomized 1:1 to either olaparib (300 mg twice daily) or placebo, both given with abiraterone acetate (1000 mg once daily) plus prednisone or prednisolone. The primary endpoint was rPFS (at planned primary analysis; data cutoff July 30, 2021). Prespecified secondary endpoints included patient-reported outcomes evaluating health-related quality of life (HRQoL; Functional Assessment of Cancer Therapy-Prostate [FACT-P]) and pain (Brief Pain Inventory-Short Form [BPI-SF]) (prespecified final analysis of overall survival; data cutoff October 12, 2022).

Key findings and limitations: Between October 31, 2018 and March 11, 2020, 1103 patients were screened, of whom 399 were randomized to olaparib + abiraterone and 397 to placebo + abiraterone. There were no overall differences between the treatment arms in the least-squares mean change from baseline in FACT-P total score or subscales, or in BPI-SF scores for worst pain, pain severity, and pain interference.

Conclusions and clinical implications: In PROpel, there were no differences in HRQoL or pain scores reported by patients with mCRPC receiving olaparib + abiraterone versus placebo + abiraterone, suggesting that patients can derive a clinical benefit from olaparib + abiraterone while maintaining similar HRQoL in comparison with current standard-of-care treatment. The PROpel trial is registered on ClinicalTrials.gov as NCT03732820.

Keywords: Abiraterone; Brief Pain Inventory-Short Form; Functional Assessment of Cancer Therapy-Prostate; Health-related quality of life; Metastatic castration-resistant prostate cancer; Olaparib, Patient-reported outcomes; PROpel trial.