“Right now, the paradigm for most patients is the hormonal approach as the first-line approach for mCRPC,” said Saad. The key takeaway from the ALSYMPCA trial, the iEAP, and the posthoc analysis is the importance of identifying patients as early as possible who will be able to receive all 6 doses of radium-223, Saad said. The median time to first SSE was 18 months. Of the enrolled patients, data from 486 (70%) were censored and the median OS in the 30% of patients treated with radium-223 was 16 months. The iEAP included patients with CRPC and more than 2 bone metastases researchers followed them for 6 months following treatment. “This study included patients who received radium-223 in a contemporary setting where we now have access to other drugs on top of radium-223, such as abiraterone acetate (Zytiga) and enzalutamide (Xtandi), &lrm which were not available when the pivotal phase III study was done,” explained Saad. Patients who had been previously treated with novel agents were permitted in this study. The phase IIIb iEAP included both symptomatic and asymptomatic patients. Patients were randomized in a 2:1 ratio to receive 1 to 6 injections of radium-223 at 50 KBq/kg plus best standard of care or placebo combined with best standard of care. The study included patients with CRPC and more than 2 symptomatic skeletal events (SSE) however, patients with known visceral metastases or those who or were unfit for, or progressed on, docetaxel were not included. The international, prospective, double-blind, randomized ALSYMPCA trial was the basis of the FDA’s 2013 approval of radium-223 in CRPC. “These are parameters that help us to figure out how to target patients more likely to get 5 or 6 cycles and, on the flip side, not wait too long to treat because then we are unlikely to give what we think is the most effective form and dose of radium-223,” added Saad, who is medical director, Interdisciplinary Urologic Oncology Group, chair, Prostate Cancer Research, University of Montreal Hospital Centers. “We looked at what parameters predicted receiving 5 or 6 cycles and, as expected, patients who were healthier earlier in the disease continuum were more likely to get the full 6 cycles of radium-223,” lead investigator Fred Saad, MD, said in an interview with OncLive. In the ALSYMPCA trial analysis, lower LDH, higher albumin, and lower log PSA levels were associated with a greater likelihood of receiving all 6 cycles of radium-223. The analysis showed that 5 to 6 injections was associated with longer OS ( P <.0001). ![]() The analysis of the iEAP showed that the ability to receive 5 to 6 injections was associated with less pain (none-mild vs moderate-severe P <.0001), lower ECOG score (0-1 vs ≥2 P =. In ALSYMPCA, the median OS was 6.2 months in patients with 1 to 4 injections and 17.9 months in patients with 5 to 6 injections. In the iEAP, the median OS was 6.3 months in patients who received 1 to 4 injections of radium-223 and not yet been reached in patients who received 5 to 6 injections. In the ALSYMPCA trial, 163 patients received 1 to 4 doses and 436 received 5 to 6 doses of radium-223. ![]() Of those patients, 223 received 1 to 4 doses, while 473 received 5 to 6 doses of radium-223 in the iEAP. In the ALSYMPCA trial, 599 patients received radium-223 and 302 received placebo in the single-arm iEAP, 696 patients received radium-223. The analysis, presented at the 2016 ASCO Annual Meeting, looked at patients from the phase IIIb International Expanded Access Program (iEAP) and the ALSYMPCA trials, both of which included patients with mCRPC who have bone metastases. The 6-dose regimen has been associated with significantly longer overall survival (OS) when compared with 1- to 4-dose regimens of radium-223 in mCRPC. In metastatic castration-resistant prostate cancer (mCRPC), pain and hemoglobin levels, PSA levels, and ECOG performance status may predict which patients will be able to receive the recommended 6-dose regimen of radium-223 dichloride (Xofigo), according to a recent posthoc analysis of 2 trials.
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