ALSYMPCA Subgroup Analysis: Radium-223 Survival Benefit Irrespective of Prior Docetaxel in Castration-Resistant Prostate Cancer With Bone Metastases
The phase III ALSYMPCA trial showed that radium-223 (Xofigo) increased overall survival vs placebo patients with castration-resistant prostate cancer and symptomatic bone metastases. In a prespecified subgroup analysis reported in The Lancet Oncology, Hoskin et al found that overall survival was increased with radium-223 treatment in both patients with and without prior docetaxel treatment. Improvements in secondary efficacy outcomes were also observed irrespective of previous docetaxel treatment.
In the double-blind ALSYMPCA trial, 921 patients with symptomatic castration-resistant prostate cancer, at leas two symptomatic bone metastases, and no known visceral metastases were randomly assigned 2:1 to receive six monthly injections of radium-223 or placebo. In total, 526 patients (57%), including 352 in the radium-223 group and 174 in the placebo group, had received prior docetaxel and 395 were unsuitable for or declined docetaxel, including 262 in the radium-223 group and 133 in the placebo group.
Overall Survival, Other Efficacy Outcomes
Radium-223 prolonged median overall survival vs placebo among both patients with prior docetaxel use (14.4 vs 11.3 months, hazard ratio [HR] = 0.70, P = .002) and patients with no prior docetaxel (16.1 vs 11.5 months, HR = 0.69, P = .01).
Radium-223 significantly prolonged median time to first symptomatic skeletal event among patients with prior docetaxel use (13.5 vs 7.8 months, HR = 0.62, P = .0009) but not among those with no prior docetaxel (17.0 vs 19.5 months, HR = 0.74, P = .12). Among both patients with and without prior docetaxel, radium-223 was associated with significant prolongation of median time to increased total alkaline phosphatase concentration (HR = 0.16, P < .0001; HR = 0.18, P < .0001) and median time to increased prostate-specific antigen concentration (HR = 0.74, P = .01; HR = 0.52, P < .001) and with a higher rate of ≥ 30% decrease in total alkaline phosphatase (48% vs 5%, P < .001; 46% vs 1%, P < .001).
Adverse Events
Grade 3 or 4 adverse events occurred in 62% of patients with prior docetaxel treatment and in 54% of those without prior docetaxel. The frequency of grade 3 or 4 thrombocytopenia was higher in radium-223 patients (9% vs 3%) among patients with prior docetaxel treatment and more similar in the two treatment groups among those without prior docetaxel (3% vs 1%). The frequencies of grade 3 or 4 anemia and neutropenia were similar between the two treatments among both docetaxel subgroups.
The investigators concluded: “Radium-223 is effective and well tolerated in patients with castration-resistant prostate cancer and symptomatic bone metastases, irrespective of previous docetaxel use.”
Peter Hoskin, MD, of Mount Vernon Cancer Centre, Northwood, Middlesex, is the corresponding author for The Lancet Oncology article.
The study was funded by Algeta ASA and Bayer HealthCare Pharmaceuticals. For full disclosures of the study authors, visit www.thelancet.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
