Results of Early Access Program for Overall Survival in Metastatic Castration-Resistant Prostate Cancer

Chicago—The results of an early access program (EAP) of patients with metastatic castration-resistant prostate cancer (mCRPC) receiving radium-223 dichloride (Ra-223) were presented during a poster session at the ASCO 2015 Annual Meeting by Fred Saad and colleagues [J Clin Oncol. 2015;33; abstract 5034]. The poster was titled Radium-223 in an international early access program (EAP): Effects of concomitant medication on overall survival in metastatic castration-resistant prostate cancer (mCRPC) patients.

The pivotal ALSYMPCA study reported improved overall survival (OS) in bone symptomatic mCRPC patients treated with Ra-223 compared with placebo (14.9 vs 11.6 months, respectively; hazard ratio [HR], 0.7). The current prospective, phase 3b study included 696 mCRPC patients from 14 countries with symptomatic or asymptomatic bone metastases with no visceral disease. Patients were randomized to receive Ra-223 50 kBq/kg via intravenous injection every 4 weeks for six cycles.

The study’s primary end points were safety and OS. The effects of concomitant medications, baseline pain, alkaline phosphatase (ALP), and Eastern Cooperative Oncology Group (ECOG) performance status on OS were also assessed.

Of the 696 patients, 58% received all six Ra-223 injections. At baseline the median age of patients was 72 years, and 88% of patients had an ECOG score of zero or one. At baseline, patient-reported pain levels were 21% no pain, 52% mild−moderate pain, and 27% severe pain. Sixty percent of patients had received prior therapy with docetaxel.

For patients treated with concomitant therapy, 22% were treated with abiraterone, 20% with denosumab, 18% with bisphosphonates, and 4% with enzalutamide.

At the time of analysis, the median OS was 16 months, and the median time to first symptomatic skeletal event was 18 months. In addition, 24% of patients had a 50% or greater confirmed ALP decrease from baseline, and 8% had a greater than 50% confirmed prostate-specific antigen decrease from baseline.

Grade 3 and 4 treatment-related adverse events (AEs) were reported in 38% of patients, and 21% discontinued treatment with Ra-223 due to AEs.

The researchers concluded, “In Ra-223 treated [patients], OS appeared to be better in those treated concomitantly with denosumab or abiraterone. Significantly longer OS was observed in [patients] with a good ECOG [performance score], no pain, and low ALP.”

Source: Saad F, Carles J, Gillessen S, et al. Radium-223 in an international early access program (EAP): Effects of concomitant medication on overall survival in metastatic castration-resistant prostate cancer (mCRPC) patients. Abstract of poster presentation at the American Society of Clinical Oncology 2015 Annual Meeting, Chicago, Illinois, May 30, 2015.