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
Prostate Cancer
Presenter Chris Parker
Authors C. Parker1, R.E. Coleman2, N. Vogelzang3, S. Nilsson4, A.J. Lloyd5, K. Staudacher6, R. Van Gool7, A.O. Sartor8
  • 1Academic Urology, The Royal Marsden NHS Foundation Trust, SM2 5PT - Sutton/UK
  • 2Academic Unit Of Clinical Oncology, Weston Park Hospital, Sheffield/UK
  • 3Developmental Therapeutics, Comprehensive Cancer Centers of Nevada, Las Vegas, Nevada/US
  • 4Radiumhemmet, Karolinska University Hospital, Stockholm/SE
  • 5Patient Reported Outcomes, Oxford Outcomes, OX1 1LE - Oxford/UK
  • 6Medical, Algeta ASA, Oslo/NO
  • 7Global Market Access, Bayer Health Care, Berlin/DE
  • 8Department Of Medicine And Urology, Tulane Cancer Center, New Orleans/US

Abstract

Introduction

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)
FACT-P*
Physical well-being -0.93 -1.65 0.047
Emotional well-being -0.12 -1.27 <0.001
Functional well-being -1.15 -2.23 0.011
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
EQ-5D*
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.