Dr Agarwal on the Benefit of PARP Inhibitors vs Chemotherapy in mCRPC

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 benefit of PARP inhibitors compared with chemotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC).

In patients with mCRPC, PARP inhibitor therapy alone or in combination with androgen receptor pathway inhibitors, such as enzalutamide (Xtandi) or abiraterone (Zytiga), are well tolerated if adverse effects (AEs) are caught early, Agarwal begins. When treating patients with PARP inhibitors, dosing is extremely important, Agarwal says. Most of the AEs associated with PARP inhibitors, such hematologic or gastrointestinal AEs, happen early in treatment, within the first 3 or 4 months, he explains. Although most patients who receive PARP inhibitors can continue treatment at the full doses, reducing the dose of PARP inhibitors in patients who experience grade 3 or 4 AEs is one strategy to manage these toxicities, Agarwal adds.

The toxicity profile of PARP inhibitors is different from that of chemotherapy. Chemotherapy-associated AEs are predictable, and most patients will experience cumulative AEs with these agents, meaning the more chemotherapy cycles they receive, the more AEs they will accumulate over time, Agarwal expands. From that perspective, PARP inhibitors are generally better tolerated than chemotherapy, he says.

Another advantage of PARP inhibitors is that they are oral pills. Patients who receive PARP inhibitors do not need to spend hours at cancer centers, which often involves traveling long distances multiple times a month, Agarwal continues. Instead, patients can undergo monitoring at local laboratories and live relatively independent lifestyles, Agarwal explains.

Many other prostate cancer therapies are under investigation, but time will tell how those novel therapies compare with PARP inhibitors, Agarwal notes. At this time, PARP inhibitors, either alone or in combinations, should be used prior to chemotherapy for eligible patients with mCRPC, Agarwal concludes.