title: Time to disease-related pain and first opioid use in patients with metastatic castration-resistant prostate cancer treated with sipuleucel-T.
abstract: BACKGROUND
  Sipuleucel-T has demonstrated improved overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). This analysis examined the effect of sipuleucel-T on time to disease-related pain (TDRP) and time to first use of opioid analgesics (TFOA) in mCRPC using data pooled from three randomized phase III studies in men with asymptomatic or minimally symptomatic mCRPC (D9901 (NCT00005947), D9902A (NCT01133704), D9902B (IMPACT; NCT00065442)).
  
  
  METHODS
  Four-hundred and twenty-eight asymptomatic patients were analyzed for TDRP; 737 patients were analyzed for TFOA. Pain status was collected using logs adjudicated by blinded, independent reviewers. Opioid use for cancer-related pain was identified from medically reviewed reports of concomitant medication. Disease-related pain was defined as pain post enrollment. TDRP and TFOA were analyzed using the Kaplan-Meier method and Cox regression.
  
  
  RESULTS
  Treatment with sipuleucel-T was not associated with a significant difference in TDRP (hazard ratio (HR)=0.819; 95% confidence interval (CI): 0.616-1.089; P=0.170; median TDRP 5.6 months for sipuleucel-T and 5.3 months for control, respectively), although 39.3% of sipuleucel-T-treated patients and 18.9% of control patients were pain-free at 12 months. However, there was a significant delay in TFOA with sipuleucel-T (HR=0.755; 95% CI: 0.579-0.985; P=0.038). Median TFOA for sipuleucel-T was 12.6, and 9.7 months for control, with 50.6% and 43.1% opioid-free at 12 months, respectively. Kaplan-Meier curves for both end points began to diverge at 6 months.
  
  
  CONCLUSIONS
  Sipuleucel-T was associated with longer TFOA but not significantly longer TDRP. Both end points demonstrated evidence of a delayed treatment effect, consistent with an active immunotherapy.
authors: Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA.
authors: E J
authors: EJ
authors: Small
authors: Departments of Oncology and Urology, School of Medicine, University of Washington, Seattle, WA, USA.
authors: C S
authors: CS
authors: Higano
authors: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors: P W
authors: PW
authors: Kantoff
authors: Dendreon Corporation, Seattle, WA, USA.
authors: J B
authors: JB
authors: Whitmore
authors: Dendreon Corporation, Seattle, WA, USA.
authors: M W
authors: MW
authors: Frohlich
authors: Smilow Cancer Center, Yale University, New Haven, CT, USA.
authors: D P
authors: DP
authors: Petrylak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D017326:Clinical Trials, Phase III as Topic; D018450:Disease Progression; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D010146:Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D014020:Tissue Extracts / Q000627:therapeutic use*
chemical_list: D000701:Analgesics, Opioid; D000970:Antineoplastic Agents; D014020:Tissue Extracts; C511774:sipuleucel-T