William Oh, MD, of Mount Sinai School of Medicine, New York, posed some questions about the first-in-class alpha emitter radium-223 chloride.

“Is this an anticancer drug or a bone-targeted drug?” he said. “With abiraterone acetate (Zytiga) and enzalutamide (Xtandi), we see declines in PSA—an anticancer biomarker we rely on—that were not shown with radium-223. We have also not seen evidence that this agent is killing cancer in the bone. So there is an important biologic question about how radium-223 is inducing a survival benefit.”

Other questions, he continued, are who should receive it and when should it be administered? In the ALSYMPCA trial, all patients had bone metastases but no visceral metastases. In actual clinical practice, many patients have both. Should the drug be given to this group? If the drug is beneficial to patients deemed “unfit for chemotherapy,” as were included in this study, what is the definition of that?

In determining the optimal time to give radium-223, there are lessons to be learned from other radiopharmaceuticals, he said. “We don’t routinely use the other radiopharmaceuticals, partly because they are not as good. But did they fail because they were used too late? We have learned that if you use radiopharmaceuticals earlier, they may have more value.” ■

Disclosure: Dr. Oh is a consultant for Bayer, Janssen, Medivation, Millennium, Astellas, and Dendreon. He has received research funding from Millennium.