title: Efficacy and Safety of Radium-223 Dichloride in Symptomatic Castration-resistant Prostate Cancer Patients With or Without Baseline Opioid Use From the Phase 3 ALSYMPCA Trial.
abstract: The phase 3 ALSYMPCA trial enrolled metastatic castration-resistant prostate cancer patients with or without baseline opioid use.
  
  
  
  To assess the efficacy and safety of radium-223 dichloride (radium-223) versus placebo in ALSYMPCA patients by baseline opioid use.
  
  
  
  Nine hundred and twenty one patients enrolled at 136 centers globally.
  
  
  
  Radium-223 (50 kBq/kg, intravenous injection) every 4 wk for six cycles or matching placebo, each plus best standard of care.
  
  
  
  Primary endpoint (overall survival [OS]), main secondary efficacy endpoints, and safety were evaluated by baseline opioid use. Additional analyses included time to first opioid use, time to first external beam radiation therapy for bone pain, and safety of concomitant external beam radiation therapy.
  
  
  
  At baseline, 408 (44%) patients had no pain and no analgesic use or mild pain with nonopioid therapy (World Health Organization ladder pain score 0-1 [nonopioid subgroup]), and 513 (56%) had moderate pain with occasional opioids or severe pain with regular daily opioids (World Health Organization ladder pain score 2-3 [opioid subgroup]). Radium-223 significantly prolonged OS versus placebo in nonopioid (hazard ratio [HR]=0.70; 95% confidence interval [CI]: 0.52-0.93; p=0.013) and opioid (HR=0.68; 95% CI: 0.54-0.86; p=0.001) subgroups, and significantly reduced risk of symptomatic skeletal events versus placebo, regardless of baseline opioid use (nonopioid subgroup: HR=0.56, 95% CI: 0.39-0.82, p=0.002; opioid subgroup: HR=0.72, 95% CI: 0.53-0.98, p=0.038). Time to first opioid use for bone pain was significantly delayed with radium-223 versus placebo (HR=0.62, 95% CI: 0.46-0.85, p=0.002). Adverse event incidences were similar between opioid subgroups.
  
  
  
  Radium-223 versus placebo significantly prolonged OS and reduced symptomatic skeletal event risk with a favorable safety profile in castration-resistant prostate cancer patients with symptomatic bone metastases, regardless of baseline opioid use.
  
  
  
  In this ALSYMPCA opioid subgroup analysis, baseline symptom levels did not appear to impact radium-223 dichloride efficacy or safety.
authors.affiliation: Royal Marsden Hospital, Sutton, London, UK. Electronic address: chris.parker@rmh.nhs.uk.
authors.forename: Christopher
authors.initials: C
authors.lastname: Parker
authors.affiliation: Cancer Treatment Centers of America, Tulsa, OK, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Finkelstein
authors.affiliation: Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Michalski
authors.affiliation: Center for Cancer Research and Cell Biology, Queen's University, Belfast, UK.
authors.forename: Joe M
authors.initials: JM
authors.lastname: O'Sullivan
authors.affiliation: Norwegian Radium Hospital, Oslo, Norway.
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Bruland
authors.affiliation: Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Vogelzang
authors.affiliation: University of Sheffield, Sheffield, South Yorkshire, UK.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Coleman
authors.affiliation: Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Sten
authors.initials: S
authors.lastname: Nilsson
authors.affiliation: Tulane Cancer Center, New Orleans, LA, USA.
authors.forename: Oliver
authors.initials: O
authors.lastname: Sartor
authors.affiliation: Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA.
authors.forename: Monica A
authors.initials: MA
authors.lastname: Seger
authors.affiliation: St. James University Hospital, Leeds, Yorkshire, UK.
authors.forename: David
authors.initials: D
authors.lastname: Bottomley
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001859:Bone Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology / Q000556:secondary; D003131:Combined Modality Therapy / Q000379:methods; D004311:Double-Blind Method; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D064129:Prostatic Neoplasms, Castration-Resistant / Q000150:complications / Q000473:pathology; D011868:Radioisotopes / Q000008:administration & dosage / Q000009:adverse effects; D011883:Radium / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis; D063189:Symptom Assessment / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D000970:Antineoplastic Agents; D011868:Radioisotopes; C581106:radium Ra 223 dichloride; D011883:Radium
keywords: ALSYMPCA; Analgesics; Bone metastases; Bone pain; Castration-resistant prostate cancer; External beam radiation therapy; Opioids; Radium-223 dichloride; Skeletal metastases; Symptomatic