title: Lower baseline prostate-specific antigen is associated with a greater overall survival benefit from sipuleucel-T in the Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) trial.
abstract: OBJECTIVE
  To explore the prognostic and predictive value of baseline variables in 512 patients with metastatic castration-resistant prostate cancer from the phase III Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) trial who were randomized to receive sipuleucel-T or control.
  
  
  METHODS
  The most powerful of these prognostic factors, baseline prostate-specific antigen (PSA), was subdivided into quartiles to evaluate treatment effect patterns. Cox regression analyses were used to assess predictors of overall survival (OS) and sipuleucel-T treatment effect within PSA quartiles. Median OS was estimated by the Kaplan-Meier method.
  
  
  RESULTS
  PSA was the strongest baseline prognostic factor (P <.0001). Furthermore, the sipuleucel-T treatment effect appeared greater with decreasing baseline PSA. The OS hazard ratio for patients in the lowest baseline PSA quartile (≤22.1 ng/mL) was 0.51 (95% confidence interval, 0.31-0.85) compared with 0.84 (95% confidence interval, 0.55-1.29) for patients in the highest PSA quartile (>134 ng/mL). Estimated improvement in median survival varied from 13.0 months in the lowest baseline PSA quartile to 2.8 months in the highest quartile. Estimated 3-year survival in the lowest PSA quartile was 62.6% for sipuleucel-T patients and 41.6% for control patients, representing a 50% relative increase.
  
  
  CONCLUSIONS
  The greatest magnitude of benefit with sipuleucel-T treatment in this exploratory analysis was observed among patients with better baseline prognostic factors, particularly those with lower baseline PSA values. These findings suggest that patients with less advanced disease may benefit the most from sipuleucel-T treatment and provide a rationale for immunotherapy as an early treatment strategy in sequencing algorithms for metastatic castration-resistant prostate cancer.
authors.affiliation: Department of Urology, Eastern Virginia Medical School of Virginia, Norfolk, VA, USA.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Schellhammer
authors.forename: Gerald
authors.initials: G
authors.lastname: Chodak
authors.forename: James B
authors.initials: JB
authors.lastname: Whitmore
authors.forename: Robert
authors.initials: R
authors.lastname: Sims
authors.forename: Mark W
authors.initials: MW
authors.lastname: Frohlich
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D019496:Cancer Vaccines / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D053208:Kaplan-Meier Estimate; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology / Q000628:therapy*; D014020:Tissue Extracts / Q000627:therapeutic use*
chemical_list: D019496:Cancer Vaccines; D006454:Hemoglobins; D014020:Tissue Extracts; C511774:sipuleucel-T; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase; D017430:Prostate-Specific Antigen