TY - JOUR
T1 - 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
AU - Parker, Christopher
AU - Finkelstein, Steven E.
AU - Michalski, Jeff M.
AU - O'Sullivan, Joe M.
AU - Bruland, Øyvind
AU - Vogelzang, Nicholas J.
AU - Coleman, Robert E.
AU - Nilsson, Sten
AU - Sartor, Oliver
AU - Li, Rui
AU - Seger, Monica A.
AU - Bottomley, David
N1 - Funding Information:
Funding/Support and role of the sponsor: ALSYMPCA was funded by Bayer AS (formerly Algeta ASA) and Bayer HealthCare Pharmaceuticals, and supported by the National Institute for Health Research Royal Marsden and Institute for Cancer Research Biomedical Research Centre. Employees of Bayer AS and Bayer HealthCare Pharmaceuticals participated in the study design and conduct and were involved in collection, management, analysis and interpretation of the data, and preparation, review, and approval of the manuscript. Heather Nyce, PhD, of SciStrategy Communications provided manuscript writing support, funded by Bayer HealthCare Pharmaceuticals.
Funding Information:
Financial disclosures: Christopher C. Parker certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Parker has received grants or funding to his institution from Bayer, has served as a consultant for BNIT, and has received honoraria from Bayer and Janssen. Finkelstein has served as a consultant for Bayer. O'Sullivan has received grants or funding from Bayer and has served as a consultant for and received honoraria from Bayer, Astellas, and Janssen. Bruland has served as a consultant (uncompensated) for Bayer and has had patents filed. Vogelzang has received grants or funding to his institution from Bayer AS (formerly Algeta ASA) and Bayer, has received honoraria from Bayer, BMS, Sanofi Aventis, Medivation, Endocyte, and Dendreon, and has a stock ownership or options interest in Caris. Coleman has received grants or funding to his institution from Bayer. Nilsson has served as a consultant for and received honoraria from Bayer HealthCare. Sartor has received grants or funding from and has served as a consultant for Bayer. Li and Seger are employed by Bayer HealthCare Pharmaceuticals. Bottomley has received grants or funding to his institution from, has served as a consultant for, and has received honoraria from Bayer.
Publisher Copyright:
© 2016 European Association of Urology
PY - 2016
Y1 - 2016
N2 - Background The phase 3 ALSYMPCA trial enrolled metastatic castration-resistant prostate cancer patients with or without baseline opioid use. Objective To assess the efficacy and safety of radium-223 dichloride (radium-223) versus placebo in ALSYMPCA patients by baseline opioid use. Design, setting, and participants Nine hundred and twenty one patients enrolled at 136 centers globally. Intervention Radium-223 (50 kBq/kg, intravenous injection) every 4 wk for six cycles or matching placebo, each plus best standard of care. Outcome measurements and statistical analysis 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. Results and limitations 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. Conclusions 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. Patient summary In this ALSYMPCA opioid subgroup analysis, baseline symptom levels did not appear to impact radium-223 dichloride efficacy or safety.
AB - Background The phase 3 ALSYMPCA trial enrolled metastatic castration-resistant prostate cancer patients with or without baseline opioid use. Objective To assess the efficacy and safety of radium-223 dichloride (radium-223) versus placebo in ALSYMPCA patients by baseline opioid use. Design, setting, and participants Nine hundred and twenty one patients enrolled at 136 centers globally. Intervention Radium-223 (50 kBq/kg, intravenous injection) every 4 wk for six cycles or matching placebo, each plus best standard of care. Outcome measurements and statistical analysis 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. Results and limitations 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. Conclusions 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. Patient summary In this ALSYMPCA opioid subgroup analysis, baseline symptom levels did not appear to impact radium-223 dichloride efficacy or safety.
KW - ALSYMPCA
KW - Analgesics
KW - Bone metastases
KW - Bone pain
KW - Castration-resistant prostate cancer
KW - External beam radiation therapy
KW - Opioids
KW - Radium-223 dichloride
KW - Skeletal metastases
KW - Symptomatic
UR - http://www.scopus.com/inward/record.url?scp=84999025082&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2016.06.002
DO - 10.1016/j.eururo.2016.06.002
M3 - Article
C2 - 27344296
AN - SCOPUS:84999025082
SN - 0302-2838
VL - 70
SP - 875
EP - 883
JO - European Urology
JF - European Urology
IS - 5
ER -