2026-04-13T01:59:59Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/57512024-12-13T10:52:50Zcom_2072_378070com_2072_378040col_2072_378092

Phase III Trial of PROSTVAC in Asymptomatic or Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer Gulley, James L. Borre, Michael Vogelzang, Nicholas J. Ng, Siobhan Parker, Chris C. Carles Galceran, Joan Agarwal, Neeraj Pròstata - Càncer - Tractament Vacunes contra el càncer Metàstasi DISEASES::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms::Prostatic Neoplasms, Castration-Resistant DISEASES::Neoplasms::Neoplastic Processes::Neoplasm Metastasis CHEMICALS AND DRUGS::Complex Mixtures::Biological Products::Vaccines::Cancer Vaccines ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales masculinos::neoplasias de la próstata::neoplasias prostáticas resistentes a la castración ENFERMEDADES::neoplasias::procesos neoplásicos::metástasis neoplásica COMPUESTOS QUÍMICOS Y DROGAS::mezclas complejas::productos biológicos::vacunas::vacunas del cáncer Càncer de pròstata; Metàstasi neoplàsica; Immunoteràpia Cáncer de próstata; Metástasis neoplásica; Inmunoterapia Prostate cancer; Metastatic neoplasm; Immunotherapy 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. Supported by Bavarian Nordic, the National Institute for Health Research Biomedical Research Centre at the Royal Marsden National Health Service Foundation Trust, and the Institute of Cancer Research. Funded in part by National Cancer Institute Cancer Center Support Grant No. P30-CA008748 and the Center for Cancer Research, National Cancer Institute. P30 CA008748/CA/NCI NIH HHS/United States DH_/Department of Health/United Kingdom 2023-11-08T10:23:17Z 2023-11-08T10:23:17Z 2023-11-08T10:23:17Z 2021-03-11T14:25:03Z 2021-03-11T14:25:03Z 2019-05-01 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/11351/5751 Journal of Clinical Oncology;37(13) https://ascopubs.org/doi/10.1200/JCO.18.02031 Attribution 4.0 International Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess American Society of Clinical Oncology Scientia