Ra-223 Dichloride in mCRPC: More Is Not Better

A multicenter, international phase II study found higher-dose and extended-dose therapy with Ra-223 did not improve survival or pain scores.

More is not better when it comes to radium-223 dichloride (Ra-223) for treating metastatic castration-resistant prostate cancer (mCRPC). Investigators of a multicenter, international phase II study have concluded that the currently approved dose and schedule of Ra-223 appear to be optimal at this time in this patient population. At the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, they reported that they had found no statistically significant benefits with extended Ra-223 compared with standard Ra-223 (abstract 5008).

“There were some clues in earlier studies of radium-223 that higher doses of radium or a longer course of it could benefit the patients. This study did not show any improvement in survival or symptomatic skeletal event–free survival,” said study coauthor Julie N. Graff, MD, from Oregon Health & Science University School of Medicine, Portland. “I am a little surprised that pain scores did not change with the higher dose or extended treatment.”

The standard dose of Ra-223 is 55 kBq/kg q4w for 6 cycles, because in the ALSYMPCA study it improved overall survival (OS) and delayed time to symptomatic skeletal events in patients with mCRPC and bone metastases. Dr. Graff and her colleagues randomized 391 patients with bone mCRPC in a 1:1:1 ratio to Ra-223 at the standard dose; Ra-223 at the high dose of 88 kBq/kg q4w for up to 6 cycles; or Ra-223 extended-dose therapy, with Ra-223 given q4w for up to 12 cycles. The researchers analyzed symptomatic skeletal events–free survival (SSE-FS) between high-dose and standard-dose treatment, as well as extended-dose and standard-dose treatment (ClinicalTrials.gov identifier: NCT02023697).

The study showed there were no statistically significant differences in SSE-FS between Ra-223 standard-dose vs high-dose therapy (median, 12.3 months vs 12.9 months; hazard ratio [HR], 1.06).  The same was true for standard-dose vs extended-dose Ra-223 (median, 13.2 months vs 10.8 months; HR, 1.26). The researchers found that the median OS was 15.8 months in the standard-dose arm, 16.0 months in the high-dose arm, and 14.4 months in the extended-dose arm.

The most common adverse events were fatigue, anemia, and nausea. The percentage of grade ≥ 3 adverse events were lowest in the standard-dose arm, at 34% (compared with rates of 48% in the high-dose arm and 53% in the extended-dose arm). “The side effects included low blood counts and fatigue. Those were not surprising. The important take-home message is to use the standard dose of radium-223 for 6 months only,” Dr. Graff told Cancer Network. “These data would suggest that a single course is plenty.”