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

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 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.

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.

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.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019 Feb 28 [Epub ahead of print]

James L Gulley, Michael Borre, Nicholas J Vogelzang, Siobhan Ng, Neeraj Agarwal, Chris C Parker, David W Pook, Per Rathenborg, Thomas W Flaig, Joan Carles, Fred Saad, Neal D Shore, Liddy Chen, Christopher R Heery, Winald R Gerritsen, Frank Priou, Niels C Langkilde, Andrey Novikov, Philip W Kantoff

1 National Institutes of Health, Bethesda, MD., 2 Aarhus Universitetshospital, Åarhus, Denmark., 3 Comprehensive Cancer Centers of Nevada, Las Vegas, NV., 4 St John of God Subiaco Hospital, Subiaco, Western Australia, Australia., 5 University of Utah Huntsman Cancer Institute, Salt Lake City, UT., 6 Royal Marsden Hospital, Sutton, United Kingdom., 7 Monash Medical Centre, Bentleigh, Victoria, Australia., 8 Herlev Hospital, Herlev, Denmark., 9 University of Colorado Cancer Center, Aurora, CO., 10 Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Barcelona, Spain., 11 Centre Hospitalier de l'Université de Montréal, Montréal, Quebec, Canada., 12 Carolina Urologic Research Center, Myrtle Beach, SC., 13 Bavarian Nordic, Morrisville, NC., 14 Radboudumc, Nijmegen, the Netherlands., 15 Centre Hospitalier Départemental, La Roche sur Yon, France., 16 Aalborg Universitethospital, Aalborg, Denmark., 17 North-Western State Medical University, Saint Petersburg, Russia., 18 Memorial Sloan Kettering Cancer Center, New York, NY.

email news signup