24th Int'l Prostate Cancer Update: Abstract - Efficacy and safety of radium-223 dichloride (radium-223) in patients who did or did not receive prior docetaxel in the phase 3 ALSYMPCA trial

VAIL, CO USA (UroToday.com) - Background: Radium-223 is the first alpha-emitter approved by both the US Food and Drug Administration and European Commission for the treatment of patients with castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastases.

In the ALSYMPCA trial, radium-223 significantly prolonged overall survival (OS) (median: 14.9 vs 11.3 mo; HR = 0.70; P < 0.001), delayed time to first symptomatic skeletal event (SSE) (median: 15.6 vs 9.8 mo; HR = 0.66; P < 0.001), and was associated with better preservation of quality of life (QOL), compared with placebo (Parker et al. N Engl J Med, 2013). Data from predefined subgroup analyses assessing efficacy and safety of radium-223 in patients who did or did not receive prior docetaxel are presented.

24th cap updateMethods: Eligible patients had progressive, symptomatic CRPC with ≥2 bone metastases; had no known visceral metastases; were receiving best standard of care; and had received prior docetaxel, or were unfit for, did not have access to, or declined docetaxel (no prior docetaxel). Patients were randomized 2:1 to 6 injections of radium- 223 (50 kBq/kg IV) q 4 wk or matching placebo and stratified by prior docetaxel use, baseline alkaline phosphatase level, and current bisphosphonate use. The primary end point was OS. Secondary end points included SSE and QOL. Subgroup efficacy data were compared using a log-rank test. QOL was assessed using the Functional Assessment of Cancer Therapy—Prostate (FACT­‐P) questionnaire, specifically designed to assess QOL in patients with prostate cancer. Interaction of prior docetaxel use with treatment effect on QOL was compared using a mixed-effects linear regression model.

Results: 395/921 (43%) randomized patients had no prior docetaxel (radium-223, n = 262; placebo, n = 133); 526/921 (57%) had received prior docetaxel (radium-223, n = 352; placebo, n = 174). Irrespective of prior docetaxel use, median OS was prolonged in the radium-223 versus placebo group (no prior docetaxel, HR = 0.75; prior docetaxel, HR = 0.71). There was a trend toward risk reduction in time to first SSE with radium-223 versus placebo, regardless of prior docetaxel use (no prior docetaxel, HR = 0.74; prior docetaxel, HR = 0.62). Similarly, the treatment effect on QOL with radium-223 was generally not influenced by prior docetaxel use. Overall, there was a low incidence of myelosuppression in both subgroups. Incidences of grade 3/4 neutropenia and thrombocytopenia were higher in prior docetaxel versus no prior docetaxel patients.

Conclusions: Regardless of prior docetaxel use, radium-223 prolonged OS and, in general, showed QOL benefit. The safety profile of radium-223 was highly favorable; patients with prior docetaxel had a higher incidence of grade 3/4 hematologic AEs than patients with no prior docetaxel.

Presented by Peter Hoskin, Mona Wahba, John Logue, David Bottomley, Sten Nilsson, Fang Fang, Jose Garcia-Vargas, Karin Staudacher, Paul Cislo, Jonathan Reuning-Scherer, and Christopher Parker at the 24th International Prostate Cancer Update - February 19 - 22, 2014 - Cascade Conference Center - Vail, Colorado USA

Mount Vernon Hospital Cancer Centre, Middlesex, UK;
Bayer HealthCare, Whippany, NJ, USA;
Christie Hospital, Manchester, UK;
St. James Hospital, Leeds, UK;
Karolinska University Hospital, Stockholm, Sweden;
Algeta ASA, Oslo, Norway;
Yale University, New Haven, CT, USA;
The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, UK

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