ASCO - Radium-223 early access program (EAP) enlightens safety, tolerability profile in a U.S. population of CRPC patients - Session Highlights

CHICAGO, IL USA ( - Radium-223, the first-approved alpha-emitting radiopharmaceutical, was safe and well-tolerated among patients with castrate-resistant prostate cancer (CRPC), regardless of prior abiraterone and/or enzalutamide use, in findings from a United States-based early access program (EAP). In this phase II, prospective, interventional, open-label, multicenter study, subjects with less prior treatment were more likely to complete the 5 to 6 of a 6-cycle injections, and thus to experience the greatest benefit.

asco xPreviously, the safety and efficacy of radium-223 vs placebo was confirmed in the phase 3 ALSYMPCA registration trial among men with CRPC and symptomatic bone metastases, with an overall survival benefit of 3.6 months (P < 0.001) and a favorable safety profile. (At the time of the ALSYMPCA trial, abiraterone and enzalutamide were not available.)

At the 2015 ASCO Annual Meeting, in Chicago, IL, principal investigator Oliver Sartor, MD, from Tulane Cancer Center, and co-investigators reported results from this EAP involving 184 patients—48 with prior abiraterone or enzalutamide; 83 with no previous abiraterone or enzalutamide treatment; and 53 patients with no prior experience with either agent. Patients with prior treatment with both agents had the greatest extent of disease and 83% with prior experience with both agents also had previous experience with docetaxel (30% of patients who were naïve to both agents).

Median overall survival of patients with either prior abiraterone or enzalutamide was similar to the overall survival of the all EAP populations, the investigators said in their ASCO publication, at 15.6 vs 17 months, respectively. Patients with prior experience with both abiraterone and enzalutamide had shorter median overall survivals of 10.7 months.

In their conclusions, the investigators noted that patients with less prior treatment were more likely to complete the cycle of 5-6 radium-223 injections and that baseline covariates that were predictive of patients receiving fewer injections (1-4 vs 5-6) were prior abiraterone and enzalutamide, an ECOG performance status of 2 or greater, and decreased baseline hemoglobin.

Prolonged overall survival was associated with receipt of 5 to 6 versus 1 to 4 radium-223 injections, in a finding that the investigators say required further validation.

Co-investigator Neal Shore, MD, Medical Director at Carolina Urologic Research Center, said of the study’s implications: “One of the most important things about the data we accumulated as a part of the early access program was that we were able to follow the patients very [closely] and very regularly—to really look for any safety signals or adverse event profiles, given the ability to have had prior therapy or concomitant [or] approved CRCP therapies. This was really important, because when we did the ALSYMPCA trials, many of these [agents] were not available for the clinicians.”

Useful trends emerged from the study. “We did see a trend among patients who had less prior treatments, less exposure to approved CRPC therapy. [These patients] actually had a likelihood of a higher survival.”

The biggest take-home message, Dr. Shore said, was that “…we did not see any new safety or adverse event signals for patients who had received radium 223, regardless of whether they had had previous abiraterone or enzalutamide treatment.” This helps to inform clinicians who are taking care of patients today and who may have access to these therapies.


Sartor O, Fernandez DC, Morris MJ, et al. Radium-223 dichloride experience in pretreated patients: early access program setting. 2015 ASCO (American Society of Clinical Oncology) Meeting. Abstract 5063.

Presented by Oliver Sartor, MD at the American Society of Clinical Oncology (ASCO) Annual Meeting - Illumination & Innovation: Transforming Data into Learning - May 29 - June 2, 2015 - Chicago, Illinois USA

Tulane Cancer Center, New Orleans, LA USA