Dr Gong on the Benefits and Limitations of PARP Inhibitor–Based Regimens 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 benefits and limitations of treatment with PARP inhibitor–based regimens for patients with metastatic castration-resistant prostate cancer (mCRPC), as well as common adverse effects (AEs) associated with these agents.

At an OncLive® State of Science Summit, Gong highlighted 3 key trials of novel PARP inhibitor combinations that have recently been approved in mCRPC. These agents represent the first targeted therapies specifically approved for this type of cancer, he reports, marking their approval as a significant advancement in the treatment space.

These combinations include olaparib (Lynparza) plus abiraterone, which was approved for patients with BRCA-mutated mCRPC in May 2023; niraparib (Zejula) and abiraterone, which gained FDA approval for the same indication in August 2023; and talazoparib (Talzenna) plus enzalutamide (Xtandi), which was granted approval for patients with homologous recombination repair gene–mutated mCRPC in June 2023.

PARP inhibitor-based combinations are highly effective and provide a targeted therapeutic approach for patients with mCRPC, Gong continues. Prior clinical trials have shown improved outcomes with these combinations, Gong states. However, despite their efficacy, these combinations are not without their limitations, he notes.

One of the major concerns with PARP inhibitor–based therapies are treatment-related AEs, he reports. The most common and clinically relevant AE observed with these therapies is myelosuppression, which increases the risk of hematologic toxicities, Gong explains. More specifically, anemia poses a significant challenge for patients treated with a PARP inhibitor Gong states, adding that approximately 40% to 50% of patients will eventually require a blood transfusion. This is a substantial proportion of patients and underscores the importance of vigilant monitoring and proactive management, he emphasizes.

Timely interventions, such as dose adjustments or supportive care measures, are needed to mitigate the impact of anemia and other hematologic AEs in this patient population, Gong concludes.