Ra-223 (Alpharadin)is an alpha-pharmaceutical targeting bone metastases (mets) with high-energy, short-range (< 100 ?m) alpha-particles. Currently it has been submitted to the FDA for approval, which we hope will happen by August 2013.In the phase 3, double-blind, randomized, multinational ALSYMPCA study, Ra-223 significantly improved overall survival (OS) in men with castrate resistant advanced prostate cancer (CRPC) having bone mets by a median increase of 3.6 months compared to placebo. The median OS: 14.9 vs 11.3 mo; P < 0.001; HR = 0.69; 95% CI: 0.58-0.83). An updated analysis of the SRE secondary endpoint is presented.The men in the study men had progressive, symptomatic CRPC with ? 2 bone mets on scintigraphy (a diagnostic test used in nuclear medicine, wherein radioisotopes called radiopharmaceuticals are taken internally, and the emitted radiation is captured by external detectors (gamma cameras) to form two-dimensional images and no known visceral mets (mets in organs or soft tissue). The subjects either previously received docetaxel, or did not because they were docetaxel ineligible, or refused docetaxel. The subjects were randomized 2:1 to receive 6 injections of Ra 223 (50 kBq/kg IV) q4wk or matching placebo and stratified by prior docetaxel use, baseline alkaline phosphatase level, and current bisphosphonate use.Nine hundred and twenty one (921) men were randomized (Ra-223, n = 614; placebo, n = 307); 40% had >20 mets.
Ra-223 significantly delayed time to first skeletal related event (SRE) versus placebo by a median increase of 5.8 months (median time to SRE: 15.6 vs 9.8 mo; P < 0.001; HR = 0.66; 95% CI: 0.52-0.83).Ra-223 significantly delayed time to first SRE with a reduction in risk observed for all 4 SRE components. Despite the longer time at risk, Ra-223 patients had an approximately 50% reduction in risk for spinal cord compression. Ra-223 is an effective therapy with a highly favorable safety profile.U-235 may provide a new standard of care for treatment of CRPC patients with bone mets.Clinical trial information: NCT00699751.J Clin Oncol 31, 2013 (suppl 6; abstr 11); Nicholas J. Vogelzang, Chris Parker, Sten Nilsson, Robert Edward Coleman, C. Gillies O’Bryan-Tear, Minghua Shan, A. Oliver Sartor; Comprehensive Cancer Centers of Nevada, Las Vegas, NV; The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom; Karolinska University Hospital, Stockholm, Sweden; Weston Park Hospital, Sheffield, United Kingdom; Algeta ASA, Oslo, Norway; Bayer HealthCare, Montville, NJ; Tulane Cancer Center, New Orleans, LA
Joel T Nowak, M.A., M.S.W.