Joe O'Sullivan, MD
Radium-223 dichloride (Xofigo), given with concomitant medication, may improve overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases, according to findings from a prospective phase IIIb study.
The study looked at data from 696 patients with bone metastatic CRPC in an international expanded access program (EAP) that included. Patients received radium-223 at 50 kBq/kg via intravenous therapy (IV) injection every 4 weeks for 6 cycles. Patients were permitted to receive concomitant therapy, with 22% of those receiving concomitant therapy on abiraterone (Zytiga), 20% on denosumab, 18% on bisphosphonates, and 4% on enzalutamide (Xtandi), in addition to radium-223. Asymptomatic and symptomatic patients with mCRPC with bone metastases were included.
At the time of analysis, median OS was 16 months, and medium time to first symptomatic skeletal events (SSE) was 18 months. A hoc analysis found that OS was statistically significantly longer in patients with concomitant denosumab and concomitant abiraterone. Grade 3/4 adverse events (AEs) were reported in 38% of patients, with 21% discontinuing radium-223 due to AEs.
The EAP studied in the prospective phase IIIb trial was a follow-up to the ALSYMPCA trial, which compared the efficacy and safety of radium-223 with placebo in 921 patients with mCRPC and symptomatic bone metastases. The study demonstrated an improvement in OS for patients who received radium-223 versus placebo, with 14 months OS in patients who took radium-223 compared to 11.2 months OS in patients who took placebo. The agent also delivered an improvement in the median time to first SSE with 13.6 months and 8.4 months to first event with radium-223 versus placebo, respectively.
To better understand the takeaways from the phase IIIb trial, OncLive
spoke with one of the study’s authors, Joe O'Sullivan, MD, clinical professor, School of Medicine, Dentistry and Biomedical Sciences, Centre for Cancer Research and Cell Biology, at Queen’s University Belfast, and head of the radiation oncology and prostate cancer clinical research groups at Northern Ireland Cancer Centre.
OncLive: How did the design of this trial differ from the ALSYMPCA trial?
: The EAP was put into place after the ALSYMPCA trial, which demonstrated survival benefit for radium-223 in men with CRPC, metastatic to bone. We looked at 696 patients in the EAP who received at least one injection of radium-223. These were patients who had similar entry criteria to the ALSYMPCA trial: CRPC with a least two bone metastases, good liver and hematologic function, and a performance status of 2 or better.
Unlike in the ALSYMPCA trial, these patients did not necessarily have symptoms. Patients were offered open-label radium-223 for six injections, with one injection every 4 weeks along with whatever care they were already receiving. What is interesting about this EAP compared to the ALSYMPCA trial is that, during the ALSYMPCA trial, we did not have access to enzalutamide or abiraterone. During this EAP, these new therapeutics were available and many patients were receiving them.
How did the findings between the two trials compare?
One of the interesting findings from the EAP was that the toxicity profile of radium-223, which, overall, is fairly good, was consistent even in those receiving other therapies at the same time. The most common toxicity from the expanded trial was a 5% to 6% rate of grade 3 thrombocytopenia. There were also very low rates of anemia, similar to the ALSYMPCA trial, which was generally reversible.
It does appear from this data that patients receiving denosumab or abiraterone at the same time as radium-223 may have a better survival advantage. This data was nonrandomized, and patients were on enzalutamide or abiraterone, or denosumab based on their physicians’ choice; however, this is something worth exploring.