title: Vaccination of metastatic renal cancer patients with MVA-5T4: a randomized, double-blind, placebo-controlled phase III study.
abstract: OBJECTIVE
  The TroVax Renal Immunotherapy Survival Trial was a randomized, placebo-controlled phase III study that investigated whether modified vaccinia Ankara encoding the tumor antigen 5T4 (MVA-5T4) prolonged survival of patients receiving first-line standard-of-care (SOC) treatment for metastatic renal cell cancer.
  
  
  METHODS
  Patients with metastatic clear cell renal cancer, prior nephrectomy, and good or intermediate prognosis were randomized 1:1 to receive up to 13 immunizations of MVA-5T4/placebo in combination with either sunitinib, interleukin-2 or interferon-α. The primary end point was overall survival. Secondary end points included progression-free survival, overall response rate, and safety.
  
  
  RESULTS
  Seven hundred thirty-three patients were recruited (365 MVA-5T4 and 368 placebo). Treatment arms were well balanced for SOC and prognosis. No significant difference in the incidence of adverse events or serious adverse events was observed. No significant difference in overall survival was evident in the two treatment arms (median 20.1 months MVA-5T4 versus 19.2 months placebo; P = 0.55). The magnitude of the 5T4-specific antibody response induced by vaccination with MVA-5T4 was associated with enhanced patient survival. Furthermore, exploratory analyses suggested a number of pretreatment hematologic factors that could identify patients who derive significant benefit from this vaccine.
  
  
  CONCLUSIONS
  MVA-5T4 in combination with SOC was well tolerated, but no difference in survival was observed in the overall study population. Exploratory analyses indicate that there may be subsets of patients who could gain significant benefit from MVA-5T4, but such results would need to be confirmed in future randomized clinical studies.
authors.affiliation: The University of Texas/Memorial Hermann Hospital, Houston, TX, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Amato
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hawkins
authors.forename: Howard L
authors.initials: HL
authors.lastname: Kaufman
authors.forename: John A
authors.initials: JA
authors.lastname: Thompson
authors.forename: Piotr
authors.initials: P
authors.lastname: Tomczak
authors.forename: Cezary
authors.initials: C
authors.lastname: Szczylik
authors.forename: Mike
authors.initials: M
authors.lastname: McDonald
authors.forename: Sarah
authors.initials: S
authors.lastname: Eastty
authors.forename: William H
authors.initials: WH
authors.lastname: Shingler
authors.forename: Jackie
authors.initials: J
authors.lastname: de Belin
authors.forename: Madusha
authors.initials: M
authors.lastname: Goonewardena
authors.forename: Stuart
authors.initials: S
authors.lastname: Naylor
authors.forename: Richard
authors.initials: R
authors.lastname: Harrop
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010919:Placebos; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome; D019444:Vaccines, DNA; D055815:Young Adult
chemical_list: D019496:Cancer Vaccines; D010919:Placebos; C504058:TroVax; D019444:Vaccines, DNA