title: Patient-reported quality-of-life analysis of radium-223 dichloride from the phase III ALSYMPCA study.
abstract: 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).
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Oncology, Karolinska University Hospital, Stockholm, Sweden sten.nilsson@ki.se.
authors.forename: S
authors.initials: S
authors.lastname: Nilsson
authors.affiliation: Bayer HealthCare, Whippany.
authors.forename: P
authors.initials: P
authors.lastname: Cislo
authors.affiliation: Departments of Medicine and Urology, Tulane Cancer Center, New Orleans.
authors.forename: O
authors.initials: O
authors.lastname: Sartor
authors.affiliation: Department of Medical Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Vogelzang
authors.affiliation: Academic Unit of Clinical Oncology, Weston Park Hospital, University of Sheffield, Sheffield.
authors.forename: R E
authors.initials: RE
authors.lastname: Coleman
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: O'Sullivan
authors.affiliation: Department of Statistics, Yale University, New Haven, USA.
authors.forename: J
authors.initials: J
authors.lastname: Reuning-Scherer
authors.affiliation: Bayer HealthCare, Whippany.
authors.forename: M
authors.initials: M
authors.lastname: Shan
authors.affiliation: Bayer HealthCare, Whippany.
authors.forename: L
authors.initials: L
authors.lastname: Zhan
authors.affiliation: Academic Urology Unit, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, UK.
authors.forename: C
authors.initials: C
authors.lastname: Parker
mesh_terms: D000368:Aged; D001859:Bone Neoplasms / Q000188:drug therapy / Q000532:radiotherapy* / Q000556:secondary; D003131:Combined Modality Therapy; D000077143:Docetaxel; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D011788:Quality of Life; D011868:Radioisotopes / Q000008:administration & dosage / Q000009:adverse effects; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000009:adverse effects; D011883:Radium / Q000008:administration & dosage* / Q000009:adverse effects; D059039:Standard of Care; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D011868:Radioisotopes; D019275:Radiopharmaceuticals; D043823:Taxoids; D000077143:Docetaxel; C581106:radium Ra 223 dichloride; D011883:Radium
keywords: castration-resistant prostate cancer; health-related quality of life; patient-reported outcomes; radium-223 dichloride; α-emitter