Dr Bilusic on the Use of PARP Inhibitors in Prostate Cancer

Marijo Bilusic, MD, PhD, genitourinary (GU) site disease group lead, GU SDD medical oncology lead, the University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, discusses key considerations and unanswered questions regarding the use of PARP inhibitors in patients with prostate cancer.

In 2023, the FDA approved 3 combinations of PARP inhibitors plus anti-androgen therapy for patients with prostate cancer, Bilusic says. Olaparib (Lynparza) in combination with abiraterone (Zytiga) and prednisone or prednisolone was approved in May 2023 for patients with BRCA-positive metastatic castration-resistant prostate cancer (mCRPC). This regulatory decision was supported by findings from the phase 3 PROpel trial (NCT03732820). Talazoparib (Talzenna) plus enzalutamide (Xtandi) was approved in June 2023 for patients with homologous recombination repair gene–mutated mCRPC based on findings from the phase 3 TALAPRO-2 trial (NCT03395197). Niraparib (Zejula) plus abiraterone acetate and prednisone received approval in August 2023 for the treatment of patients with mCRPC with deleterious or suspected deleterious BRCA mutations, a regulatory decision that was based on findings from the phase 3 MAGNITUDE trial (NCT03748641). Each of these trials demonstrated that PARP inhibitors plus anti-androgen therapy prolong radiographic progression-free survival (rPFS).

The overall survival data from these trials are not yet mature, and questions remain about the optimal role and sequencing of PARP inhibitors in prostate cancer, Bilusic explains. For instance, it is unclear whether PARP inhibitors should be used in upfront combinations to generate favorable rPFS outcomes or as monotherapy followed by anti-androgen therapy, which may improve quality of life and reduce the risk of adverse effects (AEs), Bilusic emphasizes. As data from PROpel, TALAPRO-2, and MAGNITUDE mature, they may come to address these questions, Bilusic notes. After personalized patient discussions, patients may currently receive PARP inhibitors as monotherapy or as part of combination regimens, according to Bilusic.

With a variety of FDA-approved PARP inhibitors in the armamentarium, questions arise regarding the differences between these agents, Bilusic says. These agents have yet to be directly compared in prospective clinical trials, and cross-trial comparisons should be interpreted with caution, Bilusic notes. Although meta-analyses demonstrate that olaparib, talazoparib, and niraparib are generally associated with similar efficacy outcomes and slight differences in AE profiles, current data do not show that 1 agent is more toxic than the others, Bilusic explains. Patients who received talazoparib in TALAPRO-2 required more dose reductions than patients who received niraparib in MAGNITUDE, but overall, these agents are comparable, Bilusic concludes.