Combining Radium-223 With Other Therapies May Be of Benefit in Metastatic Castration-Resistant Prostate Cancer
In an international, single-arm phase IIIB trial reported in The Lancet Oncology, Saad et al found benefit with the addition of abiraterone (Zytiga) or enzalutamide (Xtandi) to radium-223 (Xofigo) in patients with metastatic castration-resistant prostate cancer. This early-access program was carried out after completion of the pivotal ALSYMPCA trial and regulatory approval of radium-223. ALSYMPCA showed superiority of radium-223 vs placebo in patients with symptomatic bone disease.
Study Details
In this open-label trial, 696 patients received at least 1 intravenous injection of radium-223 at 50 kBq/kg (current recommendation = 55 kBq/kg after implementation of the National Institute of Standards and Technology update in April 2016); injections were given every 4 weeks for up to 6 injections. Other concomitant anticancer therapies were allowed. A total of 403 patients received all 6 injections.
Survival Outcomes
Median follow-up was 7.5 months. Median overall survival was 16 months. Exploratory analyses of overall survival showed improved survival with alkaline phosphatase concentration < vs ≥ the upper limit of normal (median = not reached vs 12 months), hemoglobin ≥ vs < 10 g/dL (median = 17 vs 10 months), Eastern Cooperative Oncology Group performance status of 0 vs 1 and vs ≥ 2 (median = not reached vs 13 months and 7 months), and no reported baseline pain vs mild pain and moderate-severe pain (median = not reached vs 14 months and 11 months). Median overall survival was longer in patients who received abiraterone, enzalutamide, or both vs none of these agents (median = not reached vs 13 months) and in those receiving vs not receiving denosumab (Xgeva; median = not reached vs 13 months).
Adverse Events
Treatment-related adverse events of any grade occurred in 281 patients (40%). The most common grade ≥ 3 treatment-related adverse events were anemia (5%), thrombocytopenia (2%), neutropenia (1%), and leukopenia (1%). Serious adverse events occurred in 35% of patients.
The investigators concluded: “Our findings show that radium-223 can be safely combined with abiraterone or enzalutamide, which are now both part of the standard of care for patients with metastatic castration-resistant prostate cancer. Furthermore, our findings extend to patients who were asymptomatic at baseline, unlike those enrolled in the pivotal ALSYMPCA study. The findings of prolonged survival in patients treated with concomitant abiraterone, enzalutamide, or denosumab require confirmation in prospective randomised trials.”
The study was funded by the Pharmaceutical Division of Bayer.
Fred Saad, MD, of the Centre Hospitalier de l’Université de Montréal, is the corresponding author of The Lancet Oncology article.
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