William K. Kelly, DO, professor of medical oncology and urology, Thomas Jefferson University, and director of the Division of Solid Tumor Oncology at Sidney Kimmel Cancer Center, discusses the next steps with the combination of radium-223 dichloride (Xofigo) and niraparib (Zejula) in metastatic castration-resistant prostate cancer (mCRPC).

Results from a phase 1b dose-finding study (NCT03076203) showed reduced prostate-specific antigen and alkaline phosphatase levels with radium-223/niraparib in chemotherapy-naïve patients with mCRPC. 

The trial evaluated an unselected patient population, explains Kelly.

A subgroup analysis of patients with DNA damage repair (DDR) alterations is being conducted to determine the efficacy of the combination in that subset of patients, says Kelly.

Additionally, an expanded phase 2 study is investigating the combination in chemotherapy-naïve patients who do not have DDR mutations, concludes Kelly.

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William K. Kelly, DO, discusses the next steps with the combination of radium-223 dichloride and niraparib in metastatic castration-resistant prostate cancer.



Dr. Kelly on the Next Steps With 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.

William K. Kelly, DO, discusses the design of a phase 1B dose-finding trial that evaluated the combination of radium-223 dichloride and niraparib in metastatic castration-resistant prostate cancer. 

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

William K. Kelly, DO, professor of medical oncology and urology, Thomas Jefferson University, and director of the Division of the Solid Tumor Oncology at Sidney Kimmel Cancer Center, discusses results from a phase 1b dose-finding study (NCT03076203) evaluating the combination of radium-223 dichloride (Xofigo) plus niraparib (Zejula) in patients with metastatic castration-resistant prostate cancer (mCRPC).

The primary objective of the trial was to determine the optimal dose of niraparib when combined with radium-223 in patients with mCRPC who have and have not received prior chemotherapy. A total of 30 patients were enrolled on the trial; 15 patients were assigned to the chemotherapy-exposed arm, while the remaining 15 patients were assigned to the chemotherapy-naïve arm. Overall, patients on both arms had an excellent ECOG performance status, says Kelly.

Results showed that the maximum-tolerated dose (MTD) of niraparib was 100 mg daily in the chemotherapy-exposed arm and 200 mg daily in the chemotherapy-naïve arm, adds Kelly. 

Interestingly, the most clinical activity with the approach was reported in in the chemotherapy-naïve arm, adds Kelly. When looking at the 200-mg dose level in a group of 7 patients who had not received prior chemotherapy, 1 patient had a ≥50% decline in prostate-specific antigen (PSA) at 12 weeks and 5 patients experienced a ≥30% decline in alkaline phosphatase (ALP). Furthermore, 43% of patients on the chemotherapy-naïve arm achieved a ≥50% reduction in ALP. Overall, all 7 patients on this arm experienced a decline in either ALP or PSA, suggesting clinical activity with this approach, concludes Kelly. 

William K. Kelly, DO, discusses results from a phase 1b dose-finding study evaluating the combination of radium-223 dichloride (Xofigo) plus niraparib (Zejula) in patients with metastatic castration-resistant prostate cancer.

William K. Kelly, DO

Articles

Dr. Kelly on the Next Steps With Radium-223 and Niraparib in mCRPC

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

Dr. Kelly on Efficacy of Radium-223 Dichloride and Niraparib in Patients With mCRPC