Dr Childs on Treatment With Olaparib Plus Abiraterone in mCRPC

Dan S. Childs, MD, medical oncologist, Mayo Clinic, discusses first-line olaparib (Lynparza) plus abiraterone (Zytiga) in patients with metastatic castration-resistant prostate cancer (mCRPC) as evaluated in the phase 3 PROpel trial (NCT03732820).

PROpel is a pivotal clinical trial designed to investigate the efficacy of olaparib in men with mCRPC who were initiating treatment following progression on androgen deprivation therapy, Childs begins. Notably, patients were enrolled irrespective of their homologous recombination repair (HRR) status, he notes. The trial employed a randomization process, assessing patients in a 1:1 ratio to receive either olaparib or placebo plus abiraterone, a standard treatment for mCRPC, Childs explains.

The primary end point of the study was radiographic progression-free survival (PFS), he continues. Additionally, overall survival (OS) was monitored as a secondary end point, Childs adds. Initial analysis of the trial results revealed an improved PFS among patients receiving olaparib compared with those receiving placebo, he imparts. However, a deeper dive into the data through subsequent analyses unveiled intriguing findings regarding the differential responses to olaparib based on genetic profiles, Childs reports.

Specifically, it was observed that the therapeutic benefit of olaparib was most pronounced in patients harboring alterations in the BRCA genes, who represented approximately 11% of the total trial population, he continues, adding that this subgroup experienced a substantial reduction in the risk of disease progression or death. Conversely, patients lacking BRCA alterations seemed to derive less pronounced benefits from olaparib treatment, highlighting the importance of genetic biomarkers in guiding personalized therapeutic decisions, Childs explains. These findings underscored the significance of molecular profiling in identifying patients who are most likely to benefit from targeted therapies such as olaparib.

Based on the evidence derived from the PROpel trial, in May 2023, the combination of olaparib and abiraterone received approval from the FDA for the treatment of patients with BRCA-mutated mCRPC, he concludes.