In a phase III trial reported in the Journal of Clinical Oncology, Gulley et al found that PROSTVAC, a viral vector-based immunotherapy, did not improve overall survival or 6-month event-free survival vs placebo in patients with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer.
PROSTVAC is an active immunotherapy vaccine containing prostate-specific antigen (PSA) as the tumor-associated antigen used to generate T-cell responses to prostate cancer.
The double-blind trial included 1,297 patients with evidence of progressive disease from 105 sites in 16 countries. 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). Randomization was stratified by PSA and lactate dehydrogenase levels.
PROSTVAC or placebo were given via subcutaneous injection at weeks 1, 3, 5, 9, 13, 17, and 21; subcutaneous GM-CSF was given on the day of immunization and for 3 consecutive days thereafter beginning with week 1, for a total of 28 doses. The first patient was screened in November 2011, and the last patient completed study treatment in July 2015.
The primary endpoint was overall survival. A secondary endpoint was event-free survival at 6 months, with events defied as radiographic progression, pain progression, chemotherapy initiation, or death. Three interim analyses were planned.
Criteria for futility were met at the third interim analysis, and the trial was stopped early.
Median overall survival was 34.4 months in arm V (hazard ratio [HR] vs placebo = 1.01, P = .47), 33.2 months in arm VG (HR vs placebo = 1.02, P = .59), and 34.3 months in the placebo group. Event-free survival at 6 months was 29.4% in arm V (odds ratio [OR] vs placebo = 0.96, 95% confidence interval [CI] = 0.71–1.29), 28.0% in arm VG (OR vs placebo = 0.89, 95% CI = 0.66–1.20), and 30.3% in arm P.
Adverse events were similar in the active treatment groups and the placebo group. The most common adverse events of any grade across all treatment groups were injection site reactions (62%–72%) and fatigue (21%–24%). Grade ≥ 3 adverse events occurred in 21% to 23% of patients. Adverse events led to treatment discontinuation in 4.9% of patients in arm V, 6.5% of patients in arm VG, and 5.8% of patients in arm P. Arrhythmias occurred in 1.4% (arm VG) to 3.5% (arm P) of patients; there were no reports of myocarditis or pericarditis. Serious treatment-related events occurred in less than 1% of all patients.
The investigators concluded, “Whereas PROSTVAC was safe and well tolerated, it had no effect on [overall survival] or [event-free survival] in metastatic castration-resistant prostate cancer. Combination therapy is currently being explored in clinical trials.”
James L. Gulley, MD, PhD, of the National Institutes of Health, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bavarian Nordic, the National Institute for Health Research Biomedical Research Centre at the Royal Marsden National Health Service Foundation Trust, the Institute of Cancer Research, and the National Cancer Institute. The study authors' full disclosures can be found at thelancet.com.
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