Patient-reported quality of life analysis of radium-223 dichloride from the phase 3 ALSYMPCA study

BACKGROUND - Radium-223 dichloride (radium-223), a first-in-class alpha-emitting radiopharmaceutical, is recommended in both pre- and post-docetaxel settings in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases based on overall survival benefit demonstrated in the phase 3 ALSYMPCA study.

ALSYMPCA included prospective measurements of health-related quality of life (QOL) using 2 validated instruments: the general EuroQoL 5D (EQ-5D) and the disease-specific Functional Assessment of Cancer Therapy-Prostate (FACT-P).

PATIENTS AND METHODS - Analyses were conducted to determine treatment effects of radium-223 plus standard of care (SOC) versus placebo plus SOC on QOL using FACT-P and EQ-5D. Outcomes assessed were percentage of patients experiencing improvement, percentage of patients experiencing worsening, and mean QOL scores during the study.

RESULTS - Analyses were performed on the intent-to-treat population of patients randomized to receive radium-223 (n=614) or placebo (n=307). Mean baseline EQ-5D utility and FACT-P total scores were similar between treatment groups. A significantly higher percentage of patients receiving radium-223 experienced meaningful improvement in EQ-5D utility score on treatment versus placebo (29.2% vs 18.5%, respectively; P=0.004; odds ratio [OR]=1.82 [95% CI 1.21-2.74]). Findings were similar for FACT-P total score (24.6% vs 16.1%, respectively; P=0.020; OR=1.70 [95% CI 1.08-2.65]). A lower percentage of patients receiving radium-223 experienced meaningful worsening versus placebo measured by EQ-5D utility score and FACT-P total score. Prior docetaxel use and current bisphosphonate use did not affect these findings. Treatment was a significant predictor of EQ-5D utility score, with radium-223 associated with higher scores versus placebo (0.56 vs 0.50, respectively; P=0.002). Findings were similar for FACT-P total score (99.08 vs 95.22, respectively; P=0.004).

The findings reported here and in the primary report of ALSYMPCA [7] suggest that in the clinical practice setting, radium-223 treatment was associated with both increased survival outcomes and clinically meaningful improvements in QOL.

CONCLUSIONS - QOL data from ALSYMPCA demonstrated that improved survival with radium-223 is accompanied by significant QOL benefits, including a higher percentage of patients with meaningful QOL improvement and a slower decline in QOL over time in patients with CRPC.

Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2016 Feb 23 [Epub ahead of print]

S Nilsson, P Cislo, O Sartor, N J Vogelzang, R E Coleman, J M O'Sullivan, J Reuning-Scherer, M Shan, L Zhan, C Parker

Karolinska University Hospital, Stockholm, Sweden., Bayer HealthCare, Whippany, NJ, USA., Tulane Cancer Center, New Orleans, LA, USA., Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA., Weston Park Hospital, University of Sheffield, Sheffield, UK., Centre for Cancer Research and Cell Biology, Queen's University Belfast, UK., Yale University, New Haven, CT, USA., Bayer HealthCare, Whippany, NJ, USA., Bayer HealthCare, Whippany, NJ, USA., The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, UK.