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 

 mutations (n = 85), according to Lattanzi. In the population of patients with 

-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 

 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 

-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

Videos

Mike Lattanzi, MD, discusses key findings from and implications of the PROpel trial in patients with metastatic castration-resistant prostate cancer.

Dr Lattanzi on the Investigation of PARP Inhibitor Combinations in mCRPC

Mike Lattanzi, MD, medical oncologist, Texas Oncology, discusses clinical trials that have evaluated the use of PARP inhibitor–based combination regimens in patients with metastatic castration-resistant prostate cancer (mCRPC).

After the efficacy of PARP inhibitor monotherapy in metastatic prostate cancer was established, 3 randomized clinical trials commenced to investigate this class of agents combined with androgen receptor pathway inhibitors in patients with mCRPC, Lattanzi says. The phase 3 PROpel trial (NCT03732820) assessed abiraterone acetate (Zytiga) in combination with olaparib (Lynparza); the phase 3 TALAPRO-2 trial (NCT03395197) studied enzalutamide (Xtandi) plus talazoparib (Talzenna); and the phase 3 MAGNITUDE trial (NCT03748641) evaluated abiraterone plus niraparib (Zejula).

MAGNITUDE was a prospective, biomarker-driven trial evaluating abiraterone in combination with niraparib and prednisone in a cohort of patients with mCRPC with homologous recombination repair (HRR) gene alterations, as well as a cohort of patients with biomarker-negative disease. The biomarker-negative cohort was closed for futility, Lattanzi notes. Subsequent analyses in the HRR-altered cohort demonstrated a significant progression-free survival benefit with the addition of niraparib to standard abiraterone and prednisone vs placebo plus abiraterone and prednisone, Lattanzi explains. At a median follow-up of 24.8 months in the 

-positive patient subgroup, the niraparib regimen elicited a median radiographic PFS of 19.5 months vs 10.9 months with placebo (HR, 0.55; 95% CI, 0.39-0.78).

Furthermore, treatment with niraparib generated improvements in time to symptomatic progression (HR, 0.54; 95% CI, 0.35-0.85) and time to initiation of cytotoxic chemotherapy (HR, 0.56; 95% CI, 0.35-0.90). A trend toward an overall survival improvement was observed in the niraparib arm (HR, 0.88; 95% CI, 0.58-1.34). Patients with 

-positive disease in the niraparib arm also experienced a trend toward delayed time to worst pain intensity (HR, 0.70; 95% CI, 0.44-1.12) and delayed time to pain interference (HR, 0.67; 95% CI, 0.40-1.12).

 plus abiraterone and prednisone for the treatment of adult patients with deleterious or suspected deleterious 

-positive mCRPC in 2023, Lattanzi concludes.

Mike Lattanzi, MD, discusses clinical trials that have evaluated the use of PARP inhibitor–based combination regimens in patients with mCRPC.

Mike Lattanzi, MD

Articles

Dr Lattanzi on Findings From the PROpel trial in mCRPC

Dr Lattanzi on the Investigation of PARP Inhibitor Combinations in mCRPC