Radium-223 Plays Important Role in Management of Prostate Cancer Subgroup

Since its approval, radium-223 for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) has been important because of the prevalence of bone metastases, according to Scott T. Tagawa, MD, MS, FACP.

At the 16th Annual Interdisciplinary Prostate Cancer Congress^® and Other Genitourinary Malignancies, Tagawa, professor of medicine and urology and medical director of the Genitourinary Oncology Research Program at Weill Cornell Medicine, reviewed data that led to radium-223 becoming the first approved alpha emitter for any type of cancer. He also spoke about trials that have demonstrated the potential survival benefits of the agent when combined and properly sequenced with hormonal therapy.

Transcript:

Radium-223 dichloride was the first alpha emitter approved for any type of cancer. It happened to be approved for patients with mCRPC and bone metastases based on the phase 3 ALSYMPCA trial [NCT00699751]. [It involved] a pseudo theranostic agent that we used as a building scan to look for the target, which is hydroxyapatite. And this potent alpha emitter, which we call a calcium emetic, is deposited into bone, mostly targeting the stroma and/or indirectly targeting tumors. Overall, that led to a survival advantage in patients with at least 2 bone [metastases] by bone scan, no known visceral metastases, and limited lymph node metastasis up to 3 centimeters.¹ That was best standard of care, which was mostly hormonal agents, steroids, or external beam alone or with the agent radium-223.

That was our first approved alpha emitter in any disease and happens to be important in prostate cancer in part because of the prevalence of bone metastases. Since that time, we’ve seen additional data with some interesting combinations, [which was] initially retrospective. It made sense that that would work because the hormonal agents are targeting different compartments. The hormonal agents such as abiraterone acetate [Zytiga] or enzalutamide [Xtandi] might also re-sensitize. And then in initial retrospective data from the expanded access program showed that if patients got radium-223 at the same time as abiraterone or enzalutamide, they live longer.

That led to what many of us thought was kind of a no-brainer phase 3 study called ERA 223 [NCT02043678]. This was in the frontline mCRPC setting in a minimally symptomatic or asymptomatic patient population. And it was abiraterone or prednisone with or without radium-223 versus placebo, with the primary end point of symptomatic skeletal event-free survival. Unfortunately, it was a flat negative study in terms of efficacy and also demonstrated significant safety concerns; there were a lot of excess fractures with that combination.² We learned from that a couple of things. One, is we shouldn’t start both drugs at the same time, and that clinical trials are important. Just because something makes sense scientifically and has retrospective data does not necessarily mean that translates into an improvement in the real world.

References

1. Hoskin P, Sartor O, O’Sullivan JM, et al. Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial. Lancet Oncol. 2014;15(12):1397-1406. doi:10.1016/S1470-2045(14)70474-7
2. Smith M, Parker C, Saad F, et al. Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(3):408-419. doi:10.1016/S1470-2045(18)30860-X