Chicago, IL—Results of a new subgroup analysis of the ALSYMPCA study that were presented at ASCO 2013 showed that radium Ra-223 dichloride (Xofigo) significantly prolongs overall survival (OS) and has a highly favorable safety profile in patients with metastatic castration-resistant prostate cancer (CRPC), regardless of whether they had previously received docetaxel therapy.
The main results of ALSYMPCA had been released previously, showing that in the overall study population of men with metastatic CRPC, Ra-223 improved median OS and delayed the time to a first skeletal-related adverse event compared with best standard of care. Based on the main results, the US Food and Drug Administration approved Ra-223 on May 15, 2013, for the treatment of patients with metastatic CRPC that has spread to the bone but not to other organs.
The ALSYMPCA trial was a phase 3, randomized, double-blind, placebo-controlled study of Ra-223 dichloride plus best standard of care compared with placebo plus best standard of care in 921 patients with late-stage CRPC with bone metastases.
Results of the New Analysis
Nicholas J. Vogelzang, MD, Executive Medical Director, Associate Chair, Developmental Therapeutics and Genitourinary Committees, US Oncology Research, Houston, TX, and Comprehensive Cancer Centers of Nevada, Las Vegas, presented the results of a prespecified subgroup analysis of patients in ALSYMPCA in a poster session. Of the 921 randomized patients included in the analysis, 395 patients had no previous treatment with docetaxel, and 526 had received previous docetaxel.
The median OS favored Ra-223 in both patient groups compared with standard of care: median OS in patients with no previous docetaxel was 16.1 months in patients who received Ra-223 versus 11.5 months with best standard of care (hazard ratio [HR], 0.745; P = .039). In patients with previous docetaxel therapy, the median OS was 14.4 months versus 11.4 months, respectively (HR, 0.71; P = .003).
The safety profile of Ra-223 in patients with CRPC that has metastasized to the bone was very favorable. Overall, there was a low incidence of myelosuppression in the docetaxel subgroups, reported Dr Vogelzang, but patients who had received previous docetaxel had a significantly higher rate of grade 3 and grade 4 bone marrow suppression with Ra-223 versus placebo (9% vs 3%, respectively; P = .01).
The total incidence of grade 3 or grade 4 thrombocytopenia was significantly higher in patients with previous docetaxel use than in patients who have not received docetaxel (7% vs 2%, respectively; P = .001).
No significant difference was found in the incidence of anemia or neutropenia between the docetaxel-receiving subgroups, or between the Ra-223 and placebo groups within each docetaxel-related subgroup.