STOCKHOLM, SWEDEN (UroToday.com) - In the ALSYMPCA trial, patients were randomized 2:1 to 6 injections of Ra-223 (50 kBq/kg IV every 4 wk) or matching placebo. The treatment period was from the first injection of study drug (week 0) to 4 weeks after the last injection (week 24). Patients were followed until 3 years after their first injection. Results of the trial showed that Ra-223 significantly improved median overall survival by 3.6 months, compared with placebo (HR = 0.70; 95% CI, 0.58-0.83; P < 0.001). ALP and PSA measurements were recorded at each treatment and follow-up visit. Patients with ALP measurements at baseline and week 12 were included in an exploratory analysis of changes in ALP levels.
Compared to patients in the placebo arm, at week 12, those who received Ra-223 treatment showed a significant decline from baseline ALP levels, which persisted during treatment and follow-up (P < 0.001). This decrease was seen in 87% (433/497) of Ra-223 patients compared with 23% (49/211) of placebo patients. On average, Ra-223 patients experienced a 32% decrease from baseline ALP, whereas placebo patients had a 37% increase (P < 0.001). Ra-223 also significantly prolonged the median time to ALP progression (7.4 vs 3.8 months; p < 0.001). Moreover, Ra-223 patients with a confirmed ALP decline at week 12 had a significantly longer median overall survival than Ra-223 patients with no confirmed ALP decline (17.8 vs 10.4 mo; HR = 0.45; 95% CI, 0.34-0.61; p < 0.0001). In regards to PSA, on average its levels increased from baseline during treatment and follow-up periods more rapidly among placebo patients than among Ra-223 patients, and also Ra-223 significantly prolonged the median time to PSA progression (HR = 0.64; 95% CI, 0.54-0.77; P < 0.001).
The U.S. Food and Drug Administration and the European Medicines Agency have approved Ra-223 as the first-in-class bone-targeted alpha-emitter for the treatment of patients with CRPC and symptomatic bone metastases (m-CRPC) and no known visceral metastases. ALP has been described and recognized as a marker of bone metastases (Nilsson, et al. Lancet Oncol, 2007; Parker, et al. Eur Urol, 2013). Unlike androgen-receptor targeting agents for which PSA can indicate effect, this study illustrates that Ra-223 primary has a major impact on ALP and, to a lesser extent, on PSA levels. Further studies are needed to evaluate ALP as a possible biomarker of response.
Presented by D. Heinrich at the 29th Annual European Association of Urology (EAU) Congress - April 11 - 15, 2014 - Stockholmsmässan - Stockholm, Sweden.
Akershus University Hospital, Department of Oncology, Lørenskog, Norway
Written by Reza Mehrazin, MD, medical writer for UroToday.com
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