Radium-223 dichloride effective in CRPC, regardless of prior docetaxel

Radium Ra 223 dichloride appeared safe and effective in patients with castration-resistant prostate cancer and symptomatic bone metastases regardless of whether they received prior docetaxel, according to a subgroup analysis from a randomized phase 3 trial.

Results of the ALSYMPCA showed radium Ra 223 dichloride [radium-223 (Xofigo, Bayer)], a targeted alpha-emitter, extended OS compared with placebo in patients with castration-resistant prostate cancer and symptomatic bone metastases. The agent also appeared well tolerated.

Researchers established prior docetaxel treatment as a trial stratification factor.

In the prespecified subgroup analysis, researchers sought to assess the effect of prior docetaxel treatment on efficacy and safety outcomes.

The subanalysis included 921 patients. Of the 526 who had undergone prior docetaxel treatment, 352 had been assigned radium-223 and 174 had been assigned placebo. Of the 395 participants who had not received docetaxel, 262 were assigned radium-223 and 133 were assigned placebo.

Subanalysis results showed radium-223 extended median OS among patients who had received docetaxel (HR=0.7; 95% CI, 0.56-0.88) and those who had not received docetaxel (HR=0.69; 95% CI, 0.52-0.92).

Other secondary benefits of radium-223, including time to first symptomatic skeletal event, were apparent across both docetaxel subgroups.

Grade 3 to grade 4 adverse events occurred in 62% of patients previously treated with docetaxel and 54% of patients who had not received docetaxel.

Among patients previously treated with docetaxel, incidence of grade 3 or grade 4 thrombocytopenia was higher in the radium-223 group than the placebo group (9% vs. 3%). Among those who had not received prior docetaxel, incidence of grade 3 or grade 4 thrombocytopenia was similar between those assigned radium-223 and those assigned placebo (3% vs. 1%).

Incidence of grade 3 or grade 4 anemia and neutropenia were comparable between study arms regardless of prior docetaxel exposure.

Despite the findings, the oncology community “needs to proceed cautiously,” Robert B. Den, MD, and W. Kevin Kelly, DO, both of Sidney Kimmel Medical College at Thomas Jefferson University, wrote in an accompanying editorial.

“The ALSYMPCA trial was not able to identify the optimum sequence of administration of docetaxel and radium-223,” they wrote. “Additionally, the trial was designed before the approval of enzalutamide (Xtandi; Medivation, Astellas) and abiraterone acetate (Zytiga, Janssen), so the clinical benefit of concomitant or sequential use of radium-223 with these drugs is unknown. Perhaps most intriguing would be the opportunity to integrate immunotherapy … with radium-223 to generate necrosis, immunogenic cell death and immune modulation.”

Still, the ALSYMPCA investigators must be commended for having the foresight to address examine the safety and efficacy of radium-223 within the context of docetaxel use, Den and Kelly wrote.

“Although these results provide clarity, many questions remain, resulting in new opportunities for exploration,” they wrote.

For more information:

Den RB. Lancet Oncol. 2014;doi:10.1016/S1470-2045(14)71026-5.
Hoskin P. Lancet Oncol. 2014;doi:10.1016/S1470-2045(14)70474-7.

Disclosure: The study was supported by Algeta and Bayer. The researchers report advisory, consultant, or speaking roles with, research support from, stock ownership in and employment relationships with Algeta ASA, Astellas, Bayer, BNIT, Janssen, Sanofi-Aventis and Takeda.