Dr. Yu on the Use of PARP Inhibitors and Radiopharmaceuticals in Prostate Cancer

Evan Y. Yu, MD, professor, medical oncology, assistant fellowship director, University of Washington School of Medicine, professor, Clinical Research Division, clinical research director, Genitourinary Medical Oncology, Fred Hutchinson Cancer Center, medical director, clinical research support, Fred Hutchinson Cancer Research Consortium, discusses new data and continuing conversations regarding the use of PARP inhibitors and targeted radioligand therapies in prostate cancer.

There is known benefit with the use of PARP inhibitors in patients with BRCA mutations, but data on their benefit in patients with other biomarkers are less robust. Accordingly, efforts to investigate the optimal use of PARP inhibitors in prostate cancer are heavily focused on the treatment of biomarker selected vs unselected populations, Yu begins.

Updated data from the phase 3 PROpel trial (NCT03732820) of first-line olaparib (Lynparza) and abiraterone acetate (Zytiga) demonstrated that the risk of disease progression or death was significantly reduced with the regimen vs placebo plus abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) Additionally, interim data from the phase 3 TRITON3 study (NCT02975934) of rucaparib (Rubraca) vs physician’s choice of docetaxel, abiraterone acetate, or enzalutamide (Xtandi) showed a significant improvement in radiographic progression-free survival with rucaparib vs investigator’s choice of therapy in the BRCA-mutant and intention-to-treat subgroups, the latter of which included patients with ATM-mutated mCRPC. Data from both trials were presented at the 2023 Genitourinary Cancers Symposium. The interpretation and application of these findings is discussion-generating and highly relevant to clinical practice, Yu says.

There is also substantial conversation regarding the emerging field of radiopharmaceuticals in prostate cancer, particularly the potential for treatment de-intensification with these agents, Yu continues. Patients are commonly prescribed intensified regimens to be administered at short, 6-week intervals, Yu states. However, some recent data indicate that stopping treatment for longer intervals and allowing the disease to slightly progress before resuming treatment can increase the maximum benefit of these agents, he explains. It will be important to educate clinicians on this potential benefit, Yu concludes.

Editor’s Note: Dr. Yu reports serving as a consultant or in an advisory role for Advanced Accelerator Applications, Bayer, Exelixis, Janssen, Merck, Oncternal Therapeutics; he reports receiving research funding from Bayer (Inst), Blue Earth Diagnostics (Inst), Daiichi Sankyo (Inst), Dendreon (Inst), Lantheus Medical Imaging (Inst); Merck (Inst), Seagen (Inst), Surface Oncology (Inst), Taiho Pharmaceutical (Inst).