Safety of Ra-223 with and without Chemotherapy in Patients with Metastatic Prostate Cancer and Bone Metastases
Radium Ra-223 dichloride (Ra-223) is an alpha-emitter that has been shown to prolong survival in patients with metastatic castrate-resistant prostate cancer (mCRPC) who have symptomatic bone metastases (Parker C, et al. N Engl J Med. 2013;369:213-223). At ESMO 2014, 2 presentations discussed the role of Ra-223 in this patient population. Morris and colleagues reported on the safety of using Ra-223 plus docetaxel versus docetaxel alone in patients with progressing mCRPC and ?2 bone metastases (Morris MJ, et al. ESMO 2014: Abstract 765PD).
A total of 46 patients were randomized in a 2:1 ratio to Ra-223 (5 × Ra-223 50 kBq/kg every 6 weeks) plus docetaxel (60 mg/m2 every 3 weeks × 10 cycles) versus docetaxel alone (75 mg/m2 every 3 weeks with a step-down option to 60 mg/m2). Safety data were collected every 3 months for up to 1 year after the start of the study. As of May 2014, 13 patients had received all planned Ra-223 plus docetaxel doses and 4 patients had received all docetaxel doses. Febrile neutropenia was reported in 2 of these 4 patients receiving docetaxel, grade 3 or 4 anemia was observed in 1 patient receiving Ra-223 plus docetaxel, and grade 1 anemia was observed in 2 patients receiving docetaxel. No thrombocytopenia was observed in either treatment group. Morris and colleagues concluded that Ra-223 plus docetaxel is a well-tolerated combination, and they intend to expand the safety cohort as originally planned.
In a related presentation, Parker and colleagues reported the long-term safety results from the ALSYMPCA trial. ALSYMPCA was a phase 3, randomized, double-blind, placebo-controlled clinical trial of patients with mCRPC and bone metastases who had previously received, declined, or were not eligible to receive docetaxel therapy (Parker C, et al. ESMO 2014: Abstract 769P).
The 921 enrolled patients received either Ra-223 (50 kBq/kg every 4 weeks) or placebo, plus best standard of care. Of the 921 patients, 574 patients were evaluable for the long-term safety follow-up (406 who had received Ra-223 and 168 who had received placebo). The median follow-up was 10.4 months for the Ra-223 group and 7.6 months for the placebo group. In the long-term safety population, 6% of the patients receiving Ra-223 and 5% of the patients receiving placebo had treatment-related adverse events. Although the incidence of myelosuppression was ?3%, leukopenia, neutropenia, or thrombocytopenia was observed in 7 patients (1.7%) in the Ra-223 group, 6 of whom had had received previous therapy with docetaxel. Thrombocytopenia was grade 1 in 2 of the 7 patients and grade 2 in another 2 patients; grade 3 leukopenia/neutropenia was seen in 2 patients, and grade 4 leukopenia was observed in 1 patient. In the placebo group, 1 patient had grade 3/4 anemia. No patients in either group had acute myeloid leukemia, myelodysplastic syndrome, or primary bone cancer.
Parker and colleagues concluded that no major hematologic safety issues were observed in the patients included in the long-term follow-up of the ALSYMPCA trial; hematologic toxicities were thought to be associated with previous docetaxel therapy and with patients with grade 3 extent of disease. None of the hematologic treatment-related adverse events affected the number of Ra-223 injections the patients received.