Combining Approved Treatments in Metastatic Castration-Resistant Prostate Cancer
Posted: Monday, May 6, 2019
The Lancet Oncology recently published what is reportedly the first randomized, controlled trial to explore the combination of two approved treatments that improve overall survival in metastatic castration-resistant prostate cancer. The ERA 223 study revealed that the addition of radium-223 to treatment with abiraterone acetate plus prednisone or prednisolone did not improve symptomatic skeletal event-free or overall survival in patients with castration-resistant prostate cancer and bone metastases. In fact, the combination also was associated with an increased frequency of bone fractures.
“We do not recommend use of this combination,” stated Matthew Smith, MD, of Massachusetts General Hospital Cancer Center, Boston, and colleagues. “As a result of our findings, the U.S. Food and Drug Administration (FDA) and the European Medicines Agency have revised prescribing recommendations for radium-223.”
The double-blind, placebo-controlled phase III international trial randomly assigned 806 chemotherapy-naive patients with castration-resistant prostate cancer and bone metastases to receive radium-223 (n = 401) or placebo (n = 405) in addition to abiraterone acetate plus prednisone or prednisolone. The study was unblinded prematurely after more fractures and deaths were noted in the radium-223 group than in the placebo group. However, all patients had already completed radium-223 or placebo therapy before this date.
At the primary analysis, 196 of 401 patients (49%) in the radium-223 group had experienced at least a single symptomatic skeletal event or died, compared with 190 of 405 patients (47%) in the placebo group. Fractures of any grade occurred in 29% and 11% of patients in the radium-223 and placebo groups, respectively. As for safety, serious treatment-emergent adverse events occurred in 160 patients (41%) in the radium-223 group and 155 patients (39%) in the placebo group.
Disclosure: The study authors’ disclosure information may be found at thelancet.com.