Dr Saad on PSA Response and Time to PSA Progression With Abiraterone Acetate and Olaparib in mCRPC

Fred Saad, MD, FRCS, principal scientist, University of Montreal Hospital Center (CHUM) Research Center (CRCHUM), head, Urology, CHUM, director, prostate cancer research, Montreal Cancer Institute/CRCHUM, full professor, Department of Surgery, Raymond Garneau Chair in Prostate Cancer, University of Montreal, discusses prostate-specific antigen (PSA) response and time to PSA progression with the combination of abiraterone acetate (Zytiga) and olaparib (Lynparza) in patients with metastatic castration-resistant prostate cancer (mCRPC).

Primary results from the phase 3 PROpel trial (NCT03732820) demonstrated improved radiographic progression-free survival with the combination of abiraterone acetate and olaparib compared with abiraterone acetate alone as frontline therapy in all-comers with mCRPC (HR, 0.66, 95% CI, 0.54-0.81; P<.001). In the trial, patients were randomly assigned 1:1 to receive 300 mg of olaparib twice daily or placebo, plus 1000 mg of abiraterone acetate once daily and 5 mg of prednisone or prednisolone twice daily until disease progression, unacceptable toxicity, or withdrawal of consent.

Post-hoc exploratory analyses presented at the 2023 AUA Annual Meeting demonstrated that first PSA response was significantly improved with the combination vs abiraterone acetate alone, reflecting an absolute difference of approximately 10%, Saad says. The chance of PSA response was 35% in patients with BRCA1/2 mutations compared with only 8% of those without mutations in the homologous recombination repair (HRR) pathway. PSA response rate was defined as the percentage of patients with a 50% reduction in PSA from baseline to lowest post-baseline result.

Time to PSA progression was also notably improved with the combination, at 35 months compared with 9 months in patients without HRR gene mutations. Time to PSA progression was defined as the time from randomization to first PSA progression per Prostate Cancer Working Group 3 criteria. Without the addition of olaparib, patients with BRCA mutations generally progress within 6 months of therapy, and to have improved time to progression to approximately 3 years in this patient population with historically aggressive disease is practice changing, Saad concludes.