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

Title: Phase III Trial of PROSTVAC in Asymptomatic or Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer.
Authors: Gulley, JL; Borre, M; Vogelzang, NJ; Ng, S; Agarwal, N; Parker, CC; Pook, DW; Rathenborg, P; Flaig, TW; Carles, J; Saad, F; Shore, ND; Chen, L; Heery, CR; Gerritsen, WR; Priou, F; Langkilde, NC; Novikov, A; Kantoff, PW
Contributors: Parker, Christopher
Publisher Information: AMER SOC CLINICAL ONCOLOGY
Publication Year: 2019
Collection: The Institute of Cancer Research (ICR): Publications Repository
Subject Terms: Humans; Neoplasm Metastasis; Granulocyte-Macrophage Colony-Stimulating Factor; Cancer Vaccines; HLA-A2 Antigen; Survival Rate; Double-Blind Method; Aged; Male; Prostatic Neoplasms; Castration-Resistant
Description: 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.
Document Type: article in journal/newspaper
File Description: Print-Electronic; 1061; application/pdf
Language: English
ISSN: 1527-7755; 0732-183X
Relation: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2019, 37 (13), pp. 1051 - 1061; https://repository.icr.ac.uk/handle/internal/3265
DOI: 10.1200/jco.18.02031
Availability: https://doi.org/10.1200/jco.18.02031; https://repository.icr.ac.uk/handle/internal/3265
Rights: https://creativecommons.org/licenses/by/4.0
Accession Number: edsbas.7F190F0B
Database: BASE