The authors performed a post hoc analysis of patients enrolled in the international early access program (iEAP) single-arm, phase 3b study of mCRPC patients (n=708) receiving up to 6 cycles of Ra-223. The primary endpoints for the study were overall survival (OS) and safety outcomes. Among the cohort, 32 % (n=228) received Ra-223 after AA and 17% (n=119) received Ra-223 concurrently with AA. Patients receiving concurrent therapy had more favorable baseline characteristics (lower ALP, lower PSA and less exposure to docetaxel) compared to patients receiving Ra-223 after AA. These clinical parameters also translated into improved performance status (ECOG 0: 42% vs 36%; ECOG 1: 47% vs 52%) for patients receiving concurrent therapy. Importantly, 26% of patients receiving concurrent therapy died during follow-up compared to 40% receiving sequential therapy, with improvement in median OS (Ra-223 after AA: 12 months; 95%CI 9.7-14.3 vs Ra223 + AA: 18.1; 95%CI 11.7 months – NR) (HR 0.56; 95%CI 0.39-0.82). Patients receiving concurrent Ra-223 + AA had fewer any grade, or serious adverse events.
In summary, healthier patients at baseline may be able to tolerate concurrent Ra-223 and AA, and may have improvement in OS compared to patients receiving Ra-223 after AA. As the authors conclude, we eagerly await the results of the ongoing ERA-223 and PEACE-3 phase 3 randomized clinically trials to further evaluate potential advantages of Ra-223 administered with AA or enzalutamide. These trials will represent patients in the chemo-naïve setting, whereas nearly ¾ of patients in the iEAP previously received docetaxel.
Presented by: Fred Saad, Department of GU Oncology, University of Montreal Hospital Center, Montreal, Canada
Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto
at the #EAU17 -March 24-28, 2017- London, England