89142-116

Overall survival benefit and safety profile of radium-223 chloride, a first-in-class alpha-pharmaceutical: Results from a phase III randomized trial (ALSYMPCA) in patients with castration-resistant prostate cancer (CRPC) with bone metastases.

Subcategory: 
Category: 
Genitourinary Cancer
Session Type and Session Title: 
Oral Abstract Session A: Prostate Cancer
General Poster Session B: Prostate Cancer
Abstract Number: 

08

Citation: 

J Clin Oncol 30, 2012 (suppl 5; abstr 8)

Author(s): 

Chris Parker, Daniel Heinrich, Joe M. O'Sullivan, Sophie D. Fossa, Ales Chodacki, Tomasz Demkow, John P. Logue, Mihalj Seke, Anders Widmark, Dag Clement Johannessen, Sten Nilsson, Peter Hoskin, Arne Solberg, Nicholas David James, Isabel Syndikus, Andrew Cross, C. Gillies O'Bryan-Tear, Jose E. Garcia-Vargas, A. Oliver Sartor; The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom; Akershus University Hospital, Lorenskog, Norway; Centre for Cancer Research and Cell Biology, Queen's University, Belfast, Ireland; Radiumhospitalet, Oslo, Norway; Hospital Kochova, Chomutov, Czech Republic; Centrum Onkologii-Instytut im Sklodowskiej-Curie, Warsaw, Poland; Christie Hospital, Manchester, United Kingdom; Centrallasarettet Växjö, Växjö, Sweden; Norrlands University Hospital, Umeå, Sweden; Ullevål University Hospital, Oslo, Norway; Karolinska Universitettsjukhuset, Stockholm, Sweden; Mount Vernon Hospital Cancer Centre, Middlesex, United Kingdom; St. Olavs Hospital, Trondheim, Norway; Cancer Research UK Clinical Trials Unit, Institute for Cancer Studies, Birmingham, United Kingdom; Clatterbridge Centre for Oncology, Wirral, United Kingdom; PharmaNet, Hemel Hempstead, United Kingdom; Algeta ASA, Oslo, Norway; Bayer HealthCare Pharmaceuticals, Montville, NJ; Tulane Cancer Center, New Orleans, LA


Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures

Abstract: 

Background: Radium-223 chloride (Ra-223) is a first-in-class alpha-pharmaceutical targeting bone metastases (mets) with high-energy alpha-particles of extremely short range (<100 μm). ALSYMPCA, a phase III, double-blind, randomized, multinational study, compared efficacy, in terms of overall survival (OS), and safety of Ra-223 plus best standard of care (BSC) vs placebo plus BSC in patients (pts) with bone mets in CRPC. Methods: Eligible pts had progressive, symptomatic CRPC with ≥ 2 bone mets on scintigraphy and no known visceral mets; were receiving BSC; and either previously received docetaxel, were docetaxel ineligible, or refused docetaxel. Pts were randomized 2:1 to receive 6 injections of Ra‑223 (50 kBq/kg IV) q4 wks or matching placebo and stratified by prior docetaxel use, baseline alkaline phosphatase level, and current bisphosphonate use. A planned interim analysis (IA) was conducted to assess the effect of Ra-223 on the primary endpoint (OS) using a predefined threshold. Survival data were compared using a stratified log-rank test. Results: 922 pts (Ra-223, n = 615; placebo, n = 307) were randomized from 6/2008-2/2011. 445 (58%) of 809 pts in the IA data set received prior treatment with docetaxel. Ra-223 significantly improved OS in pts with CRPC with bone mets vs placebo (two-sided P = 0.00185; HR = 0.695; 95% CI, 0.552-0.875; median OS 14.0 mo vs 11.2 mo, respectively). Safety and tolerability of Ra-223 were highly favorable and showed low incidence of myelosuppression (eg, grades 3/4 neutropenia in 1.8% and 0.8% and thrombocytopenia in 4% and 2% of the Ra-223 and placebo groups, respectively). Conclusions: Ra-223 is an effective therapy that improved OS with a highly favorable safety profile, and may provide a new standard of care for the treatment of CRPC pts with bone mets.


Pts reporting adverse events (AEs), n (%) Ra-223
(n = 509*)
Placebo
(n = 253*)

All grade AEs 450 (88) 237 (94)
Grade 3 or 4 AEs 257 (51) 150 (59)
Serious AEs 220 (43) 139 (55)
Discontinued due to AEs 68 (13) 51 (20)

*Pts who received ≥1 injection.