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 BRCA-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 BRCA-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).

Based on the data from MAGNITUDE, the FDA approved niraparib plus abiraterone and prednisone for the treatment of adult patients with deleterious or suspected deleterious BRCA-positive mCRPC in 2023, Lattanzi concludes.