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

Abstract

Background: Radium-223 dichloride (radium-223), a first-in-class α-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 III ALSYMPCA study. ALSYMPCA included prospective measurements of health-related quality of life (QOL) using two 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 carried out on the intent-to-treat population of patients randomized to receive radium-223 (n = 614) or placebo (n = 307). The 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% versus 18.5%, respectively; P = 0.004; odds ratio (OR) = 1.82 [95% confidence interval (CI) 1.21-2.74]}. Findings were similar for FACT-P total score [24.6% versus 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 versus 0.50, respectively; P = 0.002). Findings were similar for FACT-P total score (99.08 versus 95.22, respectively; P = 0.004).

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.

Keywords: castration-resistant prostate cancer; health-related quality of life; patient-reported outcomes; radium-223 dichloride; α-emitter.

Figure 1.

Percentage of patients experiencing a meaningful improvement in EQ-5D utility score or FACT-P total score while on treatment (week 16 and/or week 24). EQ-5D, EuroQoL 5D; FACT-P, Functional Assessment of Cancer Therapy-Prostate. ^aA responder was defined as a patient having an increase in FACT-P total score of ≥10 from baseline at either week 16 and/or week 24. ^bA responder was defined as a patient having an increase in EQ-5D utility score of ≥0.1 from baseline at either week 16 and/or week 24.

Figure 2.

Percentage of patients experiencing a meaningful improvement in Functional Assessment of Cancer Therapy-Prostate (FACT-P) subscale scores while on treatment (week 16 and/or week 24). EWB, emotional well-being; FWB, functional well-being; PCS, prostate cancer subscale; PRS, pain-related score; PWB, physical well-being; SWB, social/family well-being. ^aA responder was defined as a patient having an increase in score of ≥3 points from baseline at either week 16 and/or week 24. ^bFor the pain-related score of the PCS, a responder was defined as a patient having an increase in score of ≥2 from baseline at either week 16 and/or week 24. A patient who initiated opioid use after baseline was assumed to be a non-responder from that time point forward.

Figure 3.

Mean change from baseline (least-squares mean ± standard error) over time in (A) EQ-5D utility score and (B) Functional Assessment of Cancer Therapy-Prostate total score. The analysis of covariance analysis was adjusted for baseline score, treatment, total alkaline phosphatase (≥ or <220 U/l), current use of bisphosphonates (yes/no), and prior use of docetaxel (yes/no).