Dr. Oh on Targeted Treatment in Metastatic Castration-Resistant Prostate Cancer

William K. Oh, MD, chief, Division of Hematology and Medical Oncology, professor of medicine and urology, Mount Sinai Hospital, and deputy director of The Tisch Cancer Institute, discusses targeted treatment in metastatic castration-resistant prostate cancer (mCRPC).

Agents that were first evaluated in relapsed/refractory settings have historically moved into earlier lines of treatment because those patients are the ones who are at the greatest risk of dying from their cancer, says Oh. The same could be true of targeted therapies that are showing promise in mCRPC. For example, olaparib (Lynparza) has shown a significant benefit in patients with mCRPC who have been exposed to first-line androgen receptor—targeted therapy. However, if a patient has a germline BRCA mutation and they present with metastatic disease, they might benefit more from a drug like olaparib up front.

As the field moves forward, up-front treatment may become more dependent on a patient’s molecular profile. For example, patients with microsatellite instability—high tumors are eligible for pembrolizumab (Keytruda). Further study may show that these patients should receive pembrolizumab up front rather than standard androgen deprivation therapy (ADT) and chemotherapy or ADT/abiraterone acetate (Zytiga). Although PARP inhibitors and checkpoint inhibitors could potentially show a greater benefit in earlier-line settings, more research is needed to validate that notion, concludes Oh.