The formal discussant of the TALAPRO-2 trial, Elena Castro, MD, PhD, took issue with the conclusion of Dr. Neeraj Agarwal and colleagues that these results support the use of talazoparib plus enzalutamide as a first-line treatment of patients with metastatic castration-resistant prostate cancer, regardless of homologous recombination repair (HRR) status. According to Dr. Castro, a better understanding is needed regarding the combination of an androgen receptor signaling inhibitor plus a PARP inhibitor, since other trials suggest the benefit is greater for patients whose cancers harbor alterations in BRCA and HRR alterations.

“We know that alterations in HRR genes sensitize patients to response to [a] PARP inhibitor, and, as Dr. Agarwal saw, there is a difference in the magnitude of the benefit for patients with and without HRR alterations. I think HRR status matters,” Dr. Castro said.

Elena Castro, MD, PhD

“Improvements in radiographic progression–free survival do not always translate to improved overall survival. The balance between side effects and potential benefit [with PARP inhibitor combination] depends on HRR status,” she stated.

“We need to remember the treatment landscape has changed. Androgen receptor pathway inhibitors [such as enzalutamide] are now the standard of care for patients with metastatic hormone-sensitive prostate cancer and nonmetastatic castration-resistant prostate cancer and may soon become the standard of care for earlier stages,” Dr. Castro said during a panel discussion after Dr. Agarwal’s presentation. “By the time they become metastatic or castration-resistant, most patients will have experienced disease progression after one of these treatments, and we don’t know whether the addition of a PARP inhibitor will induce responses in those patients.” 

DISCLOSURE: Dr. Castro has received honoraria from Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, Janssen-Cilag, Pfizer, and Roche; served as a consultant or advisor to Astellas Pharma, AstraZeneca, Bayer, Janssen, Merck, MSD Oncology, and Pfizer; received institutional research funding from Astellas Pharma, AstraZeneca, Bayer, Janssen, and Pfizer; provided expert testimony for Pfizer; and received reimbursement for travel expenses from Astellas Pharma, AstraZeneca, Bayer, Janssen, and Pfizer.