Dr Lattanzi on Findings From the PROpel trial in mCRPC

Mike Lattanzi, MD, medical oncologist, Texas Oncology, discusses key findings from, and implications of, the phase 3 PROpel trial (NCT03732820) in patients with metastatic castration-resistant prostate cancer (mCRPC).

The PROpel trial had a similar design to the phase 3 MAGNITUDE trial (NCT03748641), which evaluated the PARP inhibitor niraparib (Zejula) in combination with abiraterone acetate (Zytiga) in patients with mCRPC, Lattanzi says. PROpel was a large, randomized trial that enrolled all-comers with mCRPC; no specific biomarkers drove patient enrollment in this trial, Lattanzi notes. Patients were randomly assigned to receive abiraterone acetate alone or in combination with olaparib (Lynparza). Most patients had not received secondary hormone therapy, meaning they were classified as having castration-resistant disease based on their prior progression on single-agent androgen deprivation therapy, Lattanzi explains. The characteristics of the PROpel population differ slightly from that of real-world patients, for whom PARP inhibitor–based combinations might be considered, Lattanzi emphasizes.

Abiraterone acetate in combination with olaparib elicited a radiographic progression-free survival (rPFS) benefit vs placebo plus abiraterone acetate across all patients in the intent-to-treat (ITT) population (n =796), particularly those with BRCA mutations (n = 85), according to Lattanzi. In the population of patients with BRCA-mutated disease, the median rPFS was not yet reached vs 8 months (95% CI, 6-15) in the olaparib and placebo arms, respectively (HR, 0.24; 95% CI, 0.12-0.45). Furthermore, the trial also showed a trend toward an overall survival (OS) benefit with olaparib vs placebo in patients with BRCA mutations (HR, 0.30; 95% CI, 0.15-0.59). In the ITT population, the rPFS and OS benefits with olaparib were smaller than in the BRCA-mutant cohort (rPFS HR, 0.77 [95% CI, 0.63-0.96]; OS HR, 0.92 [95% (CI, 0.74-1.14]).

Although mature OS data have yet to read out from PROpel and other trials investigating PARP inhibitor–based combination regimens in patients with prostate cancer, the rPFS findings from PROpel supported the 2023 FDA approval of olaparib plus abiraterone acetate for patients with BRCA-mutated mCRPC, Lattanzi concludes.