898PD - Updated survival, quality of life (QOL), and safety data of radium-223 chloride (RA-223) in patients with castration-resistant prostate cancer (CRPC...
|Date||30 September 2012|
|Event||ESMO Congress 2012|
|Session||Genitourinary tumors, prostate|
|Topics|| Supportive Care
C. Parker1, R.E. Coleman2, N. Vogelzang3, S. Nilsson4, A.J. Lloyd5, K. Staudacher6, R. Van Gool7, A.O. Sartor8
Ra-223 is a first-in-class alpha-emitter pharmaceutical that targets bone metastases with high-energy, very short range (<100 µm) alpha-particles. In the interim analysis (IA) of ALSYMPCA, which compared Ra-223 and placebo (Pbo) in CRPC patients (pts) with bone metastases receiving best standard of care, Ra-223 improved overall survival (OS), with a 30.5% reduction in risk of death (HR .695). Updated survival, QOL, and safety data are reported.Methods
Eligible pts previously received or refused docetaxel, or were docetaxel ineligible, and were randomized 2:1 to receive Ra-223 (50 kBq/kg IV) or Pbo every 4 weeks x 6. After the IA, an updated analysis of all enrolled pts prior to crossover assessed effects of Ra-223 on the primary (OS, using a stratified log-rank test) and secondary (eg, skeletal-related events [SREs], QOL, and safety) endpoints. QOL was assessed with the Functional Assessment of Cancer Therapy—Prostate (FACT-P) and EuroQoL (EQ-5D) instruments.Results
The table shows the updated analysis data for 921 pts (Ra-223, n = 614; Pbo, n = 307). Median OS benefit for Ra-223 was 3.6 mos (HR 0.695). Time to first SRE was 6 mos longer with Ra-223. At week 16, Ra-223 pts reported significantly greater well-being (physical, emotional, functional, prostate cancer score, and total score) (FACT-P) and significantly better QOL (EQ-5D) compared to Pbo pts. The incidence of myelosuppression with Ra-223 was low: 2.2% grade 3/4 neutropenia; 6.3% grade 3/4 thrombocytopenia.
|Parameter||Ra-223 + BSC (n = 614)||Placebo + BSC (n = 307)||P value Hazard ratio (95% CI)|
|Median overall survival, mos||14.9||11.3||.00007 0.695 (0.581, 0.832)|
|Median time to first SRE, mos||15.6||9.8||.00037 0.658 (0.522, 0.830)|
|Prostate cancer score||-0.10||-1.74||0.012|
|Trial outcome index score||-2.14||-5.16||0.011|
|FACT-P total score||-2.53||-6.88||0.006|
|Single index utility||-0.0181||-0.0952||0.003|
*Mean change from baseline at week 16.Conclusions
The ALSYMPCA updated analysis substantiates that Ra-223 is an effective therapy that significantly improves OS and time to first SRE, with a highly favorable safety profile, in CRPC pts with bone mets. Ra-223 showed significantly better preservation of QOL, with improved functioning and well-being, compared to Pbo.Disclosure
C. Parker: C. Parker has served in a consultant or advisory role for Algeta ASA (uncompensated) and Bayer.
S. Nilsson: S. Nilsson has served in a consultant or advisory role for Algeta ASA.
N. Vogelzang: N. Vogelzang has served in a consultant or advisory role for and has received grant/research support from Algeta ASA and Bayer.
K. Staudacher: K. Staudacher is employed by and has an ownership interest in Algeta ASA.
R. van Gool: R. Van Gool is employed by and has an ownership interest in Bayer.
A.O. Sartor: O. Sartor has served in consultant or advisory roles for Algeta ASA and Bayer.
All other authors have declared no conflicts of interest.