The phase III ERA223 trial exploring radium-223 dichloride (Xofigo) plus abiraterone acetate (Zytiga) in patients with asymptomatic or mildly symptomatic chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) has been unblinded early.
Bayer, the manufacturer of radium-223, reported that the unblinding follows the recommendation of an independent data monitoring committee, which observed more fractures and deaths in patients receiving both radium-223 and abiraterone acetate compared with patients receiving abiraterone alone.
The company has updated researchers of studies with radium-223 and relevant health authorities about the unblinding, and will next update healthcare professionals. Bayer noted in its press release that new safety signals have not been observed in other studies exploring the radium-223/abiraterone combination.
“Patient safety is our top priority. We are therefore unblinding the study to thoroughly analyze the data,” Mike Devoy, member of the Pharmaceuticals’ Division Executive Committee and Chief Medical Officer at Bayer, said in a statement. “It is important to note that, based on available data from previous trials as well as real-world use, the benefit-risk profile of Xofigo in its approved indication remains favorable. We remain committed to further exploring the potential of radium-223 across multiple tumor types with significant unmet medical need, including prostate cancer.”
The double-blind ERA223 trial has accrued 806 patients with asymptomatic or mildly symptomatic chemotherapy-naïve bone predominant mCRPC. Patients were randomized in a 1:1 ratio to receive radium-223 for 6 cycles with abiraterone acetate plus prednisone/prednisolone, or placebo for 6 cycles with abiraterone acetate plus prednisone/prednisolone and best supportive care.
Treatment was administered until an on-study symptomatic skeletal event occurred, or other withdrawal criteria were met. The primary endpoint of the trial is symptomatic skeletal event–free survival.
The alpha particle-emitting radioactive therapeutic agent radium-223 is approved by the FDA for the treatment of patients with CRPC, symptomatic bone metastases and no known visceral metastatic disease. The approval is based on the ALSYMPCA trial, a phase III, double-blind, randomized, multinational study designed to compare radium-223 with placebo and best standard care in patients with CRPC and at least 2 bone metastases.
Radium-223 significantly improved overall survival (OS), with a median OS of 14.9 months compared with 11.3 months in the placebo arm (HR, 0.70; 95% CI, 0.58-0.83; P
<.001). Additionally, the time to the first skeletal-related event was a median of 15.6 months in the radium-223 arm versus 9.8 months in the placebo arm (HR, 0.66; 95% CI, 0.52-0.83; P
In 2011, the FDA approved abiraterone for use in combination with prednisone for the treatment of patients with mCRPC after docetaxel. The approval was based on the COU-AA-301 trial, which included 1195 patients with mCRPC who had previously received docetaxel.
The initial analysis showed that the median OS was 14.8 months for patients who received abiraterone compared with 10.9 months for patients receiving placebo (HR, 0.65; 95% CI, 0.54-0.77; P
<.001). An updated OS analysis, conducted after 775 events, showed a median OS of 15.8 months versus 11.2 months with abiraterone versus placebo, respectively (HR, 0.740; 95% CI, 0.638-0.859).
In 2012, the FDA approved abiraterone in combination with prednisone for use prior to chemotherapy for the treatment of men with mCRPC. Recently, Janssen Biotech, the company that develops abiraterone, submitted a supplemental new drug application to the FDA for use of abiraterone in combination with prednisone and androgen deprivation therapy for high-risk patients with metastatic hormone-naïve prostate cancer or newly-diagnosed metastatic hormone-sensitive prostate cancer.