Dr Gong on the Frontline Use of PARP Inhibitors in mCRPC

Jun Gong, MD, associate professor, medicine, medical oncologist, Gastrointestinal Disease Research Group, Pancreatic Cancer Research Group, Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai, discusses the variety of frontline PARP inhibitor–based treatment regimens that are FDA approved for patients with metastatic castration-resistant prostate cancer (mCRPC).

Three pivotal clinical trials led to the FDA approvals of 3 different PARP inhibitor–based combinations for the treatment of patients with treatment-naive mCRPC, Gong says. The phase 3 PROPEL trial (NCT03732820) evaluated the PARP inhibitor olaparib (Lynparza) in combination with the androgen receptor signaling inhibitor (ARSI) abiraterone acetate (Zytiga). The phase 3 TALAPRO-2 trial (NCT03395197) investigated the PARP inhibitor talazoparib (Talzenna) combined with the ARSI enzalutamide (Xtandi). The phase 3 MAGNITUDE trial (NCT03748641) examined the combination of the PARP inhibitor niraparib (Zejula) and abiraterone. All 3 trials demonstrated superior radiographic progression-free survival (rPFS) outcomes with the PARP inhibitor combinations vs their respective control arms. For instance, in TALAPRO-2, the median rPFS was not reached (NR; 95% CI, 27.5 months-NR) with talazoparib vs 21.9 months (95% CI, 16.6-25.1) with placebo. The median follow-up was 24.9 months (IQR, 21.9-30.2) for the talazoparib arm and 24.6 months (IQR, 14.4-30.2) for the arm of patients who received placebo plus enzalutamide.

The regimens from all 3 trials received FDA approval for use in the first-line mCRPC setting. However, the indications for these regimens have nuanced differences, Gong emphasizes. Olaparib plus abiraterone and prednisone or prednisolone was FDA approved in May 2023 for the treatment of patients with deleterious or suspected deleterious BRCA-mutated mCRPC. Niraparib plus abiraterone was granted FDA approval in August 2023 for this indication. Talazoparib plus enzalutamide received FDA approval in June 2023 for use in patients with homologous recombination repair gene–mutated mCRPC. Whereas the PROPEL and MAGNITUDE regimens are limited to patients displaying BRCA1 and BRCA2 mutations, in contrast, the TALAPRO-2 regimen has a broader FDA label and can be used in a wider array of patients, Gong concludes.