Neal Shore, MD
Prior treatment with abiraterone acetate (Zytiga) or enzalutamide (Xtandi) did not alter the survival benefit seen with radium-223 (Xofigo) in men with advanced castration-resistant prostate cancer (CRPC), an analysis of expanded-access data presented at the 2015 AUA Annual Meeting showed.
Men who received abiraterone and/or enzalutamide (n = 131) prior to radium-223 had a median overall survival (OS) of 15.6 months. The median OS was 15.6 months and 10.7 months for those treated with prior abiraterone (n = 120) and enzalutamide (n = 59), respectively. In the full population of the study (n = 184), the median OS was 17 months.
“In this extended access program, radium-223 was safe and well tolerated, regardless of prior or concurrent exposure to abiraterone and/or enzalutamide,” Neal D. Shore, MD, director of Carolina Urologic Research Center in Myrtle Beach, South Carolina, and colleagues concluded in a poster presentation.
“Overall survival was comparable in radium-223-treated patients who received prior abiraterone and/or enzalutamide versus the overall extended-access population. Initial findings of overall survival in the small numbers of patients receiving concurrent abiraterone or enzalutamide are indeterminate. Current trials are under way to assess radium-223 combinations.”
Radium-223 gained approval from the FDA in May 2013 as a treatment for men with symptomatic CRPC that had spread to the bones but not to any other organs. This decision was based on findings from the pivotal phase III ALSYMPCA trial.
At an interim analysis, the median OS was 14 months with radium-223 and 11.2 months with placebo (HR = 0.70; P
= .00185). The time to the first skeletal-related event was a median of 15.6 months in the radium-223 arm versus 9.8 months with placebo (HR = 0.658; P
The US expanded-access program for radium-223 was a prospective phase II, open-label, interventional trial for men with CRPC and bone metastases. The study was initiated to provide early access to radium-223 prior to regulatory approval.
Both abiraterone and enzalutamide were already available, and some men received one or both drugs before, during, and following the expanded-access program treatment period. Whether treatment with the newer hormonal therapies affected the safety or survival benefit of radium-223 was unclear.
Men enrolled in the expanded access program had an extensive treatment history. The data showed that 72% of men treated with abiraterone and 81% of men treated with enzalutamide also had received docetaxel. Men who received either of the hormonal therapies had higher alkaline phosphatase and prostate-specific antigen levels than did patients with no prior exposure to abiraterone or enzalutamide.
In those who received radium-223 with concurrent enzalutamide (n = 15), the median OS was 10.7 months. In the concurrent abiraterone arm (n = 25), the median OS was not estimable.
In patients in the abiraterone arm who were not treated with concurrent abiraterone (n = 159), the median OS was 15.6 months (similar to those treated with prior abiraterone). In patients who were not treated with concurrent enzalutamide (n = 169), the median OS was 17.1 months.
The 17 patients who received concurrent abiraterone and/or enzalutamide but had no prior treatment history of either hormonal therapy appeared to live longer, but the small numbers precluded definitive assessment, the authors wrote.
In the small number of patients who received concurrent abiraterone or enzalutamide, radium-223 had a safety profile similar to that observed in the overall expanded-access population. The most common treatment-emergent grade 3/4 adverse events were anemia (16% with abiraterone, 13% with enzalutamide), thrombocytopenia (4%, 0%), and back pain (0%, 13%).
Grade 3/4 adverse events were apparent in 38% of those treated with prior abiraterone and 39% of those treated with prior enzalutamide. The rate of serious adverse events and treatment discontinuation was similar between the arms.
“Safety profiles of radium-223 were similar regardless of prior exposure to abiraterone or enzalutamide,” the authors noted. “The most common grade 3/4 events were anemia and thrombocytopenia.”
In mid-October 2014, Bayer, the developer of radium, halted product in order to address the presence of fibrous particles found in the radiopharmaceutical. Production was quickly reinstated in November 2014.
This shortage period impacted the availability of the product for the expanded access program. As a result, patients in the study received radium-223 for a relatively short duration (approximately 3 to 9 months), which may have impacted the findings from the study.