title: Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer.
abstract: OBJECTIVE
  Therapeutic prostate-specific antigen (PSA) -targeted poxviral vaccines for prostate cancer have been well tolerated. PROSTVAC-VF treatment was evaluated for safety and for prolongation of progression-free survival (PFS) and overall survival (OS) in a randomized, controlled, and blinded phase II study.
  
  
  METHODS
  In total, 125 patients were randomly assigned in a multicenter trial of vaccination series. Eligible patients had minimally symptomatic castration-resistant metastatic prostate cancer (mCRPC). PROSTVAC-VF comprises two recombinant viral vectors, each encoding transgenes for PSA, and three immune costimulatory molecules (B7.1, ICAM-1, and LFA-3). Vaccinia-based vector was used for priming followed by six planned fowlpox-based vector boosts. Patients were allocated (2:1) to PROSTVAC-VF plus granulocyte-macrophage colony-stimulating factor or to control empty vectors plus saline injections.
  
  
  RESULTS
  Eighty-two patients received PROSTVAC-VF and 40 received control vectors. Patient characteristics were similar in both groups. The primary end point was PFS, which was similar in the two groups (P = .6). However, at 3 years post study, PROSTVAC-VF patients had a better OS with 25 (30%) of 82 alive versus 7 (17%) of 40 controls, longer median survival by 8.5 months (25.1 v 16.6 months for controls), an estimated hazard ratio of 0.56 (95% CI, 0.37 to 0.85), and stratified log-rank P = .0061.
  
  
  CONCLUSIONS
  PROSTVAC-VF immunotherapy was well tolerated and associated with a 44% reduction in the death rate and an 8.5-month improvement in median OS in men with mCRPC. These provocative data provide preliminary evidence of clinically meaningful benefit but need to be confirmed in a larger phase III study.
authors.affiliation: Medical Director, BN ImmunoTherapeutics, 2425 Garcia Ave, Mountain View, CA 94043, USA.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Schuetz
authors.forename: Brent A
authors.initials: BA
authors.lastname: Blumenstein
authors.forename: L Michael
authors.initials: LM
authors.lastname: Glode
authors.forename: David L
authors.initials: DL
authors.lastname: Bilhartz
authors.forename: Michael
authors.initials: M
authors.lastname: Wyand
authors.forename: Kelledy
authors.initials: K
authors.lastname: Manson
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Panicali
authors.forename: Reiner
authors.initials: R
authors.lastname: Laus
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.forename: William L
authors.initials: WL
authors.lastname: Dahut
authors.forename: Philip M
authors.initials: PM
authors.lastname: Arlen
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
authors.forename: Wayne R
authors.initials: WR
authors.lastname: Godfrey
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000276:immunology*; D004311:Double-Blind Method; D005822:Genetic Vectors / Q000276:immunology; D006801:Humans; D007114:Immunization; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009919:Orchiectomy; D011212:Poxviridae / Q000276:immunology*; D017430:Prostate-Specific Antigen / Q000037:antagonists & inhibitors / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D014614:Vaccines, Synthetic; D017430:Prostate-Specific Antigen