Dr. Kelly on Identifying Optimal Dose of Radium-223 and Niraparib in mCRPC

William K. Kelly, DO, professor of medical oncology and urology at Thomas Jefferson University, and director of the Division of the Solid Tumor Oncology at Sidney Kimmel Cancer Center, discusses the design of a phase 1B dose-finding trial (NCT03076203) that evaluated the combination of radium-223 dichloride (Xofigo) and niraparib (Zejula) in metastatic castration-resistant prostate cancer (mCRPC).

The phase 1B trial had a unique design, says Kelly. One of the biggest issues with radium-233 is that patients typically don’t experience toxicities until later on in their treatment, Kelly explains. As such, investigators used a Time-to-Event Continual Reassessment Method, referred to as TITE-CRM, to carefully analyze when these toxicities were occurring in patients with mCRPC, Kelly explains. This method was used to identify the maximum tolerated dose, in addition to all of the toxicities reported over a 12-week period, Kelly adds.

In the trial, patients received a standard dose of radium-223 and 3 dose levels of niraparib: 100 mg, 200 mg, and 300 mg daily. Patients were allowed to receive 6 cycles of radium-223 and, once they completed the combination therapy, they were able to continue taking nirapirab alone, Kelly concludes.