Phase III Trial of PROSTVAC in Asymptomatic or Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer

J Clin Oncol. 2019 May 1;37(13):1051-1061. doi: 10.1200/JCO.18.02031. Epub 2019 Feb 28.


Purpose: PROSTVAC, a viral vector-based immunotherapy, prolonged median overall survival (OS) by 8.5 months versus placebo in metastatic castration-resistant prostate cancer in a phase II study. This phase III study further investigated those findings.

Patients and methods: Patients were randomly assigned to PROSTVAC (Arm V; n = 432), PROSTVAC plus granulocyte-macrophage colony-stimulating factor (Arm VG; n = 432), or placebo (Arm P; n = 433), stratified by prostate-specific antigen (less than 50 ng/mL v 50 ng/mL or more) and lactate dehydrogenase (less than 200 v 200 U/L or more). Primary end point was OS. Secondary end points were patients alive without events (AWE)-namely, radiographic progression, pain progression, chemotherapy initiation, or death-at 6 months and safety. The study design was a superiority trial of PROSTVAC (Arm V or Arm VG) versus Arm P. Three interim analyses were planned.

Results: At the third interim analysis, criteria for futility were met and the trial was stopped early. Neither active treatment had an effect on median OS (Arm V, 34.4 months; hazard ratio, 1.01; 95% CI, 0.84 to 1.20; P = .47; Arm VG, 33.2 months; hazard ratio, 1.02; 95% CI, 0.86 to 1.22; P = .59; Arm P, 34.3 months). Likewise, AWE at 6 months was similar (Arm V, 29.4%; odds ratio, 0.96; 95% CI, 0.71 to 1.29; Arm VG, 28.0%; odds ratio, 0.89; 95% CI, 0.66 to 1.20; placebo, 30.3%). Adverse events were similar for the treatment and placebo groups, with the most common being injection site reactions (62% to 72%) and fatigue (21% to 24%). Arrhythmias were the most common cardiac-related events (1.4% to 3.5%). There were no reports of either myocarditis or pericarditis. Serious treatment-related events occurred in less than 1% of all patients.

Conclusion: Whereas PROSTVAC was safe and well tolerated, it had no effect on OS or AWE in metastatic castration-resistant prostate cancer. Combination therapy is currently being explored in clinical trials.

Trial registration: NCT01322490.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / adverse effects
  • Double-Blind Method
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / adverse effects
  • HLA-A2 Antigen / immunology
  • Humans
  • Male
  • Neoplasm Metastasis
  • Prostatic Neoplasms, Castration-Resistant / immunology
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Prostatic Neoplasms, Castration-Resistant / therapy*
  • Survival Rate


  • Cancer Vaccines
  • HLA-A2 Antigen
  • Granulocyte-Macrophage Colony-Stimulating Factor

Associated data