Dr Agarwal on Advances With PARP Inhibitors in Prostate Cancer

Neeraj Agarwal, MD, professor, medicine, Presidential Endowed Chair, Cancer Research, director, Genitourinary Oncology Program, director, Center of Investigational Therapeutics, Huntsman Cancer Institute, University of Utah, discusses the role of PARP inhibitors in metastatic castration-resistant prostate cancer (mCRPC) and the potential evolutions of the mCRPC and metastatic castration-sensitive prostate cancer (mCSPC) treatment paradigms.

The phase 3 PROpel trial (NCT03732820) investigated abiraterone acetate (Zytiga) plus the PARP inhibitor olaparib (Lynparza) and prednisone or prednisolone vs abiraterone acetate plus placebo and prednisone or prednisolone in the frontline setting in patients with mCRPC. Findings from this trial led to the May 2023 FDA approval of the combination in patients with mCRPC harboring BRCA1/2 mutations. In addition, in December 2022, the combination was approved in the European Union for adult patients with mCRPC who are not eligible for chemotherapy.

The phase 3 TALAPRO-2 trial (NCT03395197) evaluated the efficacy and safety of the PARP inhibitor talazoparib (Talzenna) or placebo plus enzalutamide (Xtandi) as first-line therapy in patients with mCRPC receiving androgen deprivation therapy. Based on the findings from this trial, talazoparib plus enzalutamide was approved by the FDA in June 2023 for patients with mCRPC harboring any homologous recombination repair (HRR) gene mutation.

The phase 3 MAGNITUDE trial (NCT03748641) investigated the addition of the PARP inhibitor niraparib (Zejula) to abiraterone acetate and prednisone in patients with mCRPC with or without HRR gene alterations. In February 2023, a new drug application seeking the approval of this combination in patients with BRCA-mutated mCRPC was submitted to the FDA.

Other large phase 3 prostate cancer trials have completed accrual or will soon complete accrual, Agarwal says. The ongoing phase 3 TALAPRO-3 trial (NCT04821622) is evaluating talazoparib or placebo plus enzalutamide in patients with HRR-mutated mCSPC. Additionally, the phase 3 AMPLITUDE trial (NCT04497844), which is currently enrolling, is investigating abiraterone acetate and prednisone with or without niraparib in patients with HRR-mutated mCSPC. Based on the positive data with these combination in the mCRPC setting, TALAPRO-3 and AMPLITUDE may also be positive and eventually influence the frontline treatment setting for patients with prostate cancer, Agarwal concludes.