IMPORTANCE: DCVAC/PCa is an active cellular immunotherapy designed to initiate an immune response against prostate cancer. OBJECTIVE: To evaluate the efficacy and safety of DCVAC/PCa plus chemotherapy followed by DCVAC/PCa maintenance treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). DESIGN, SETTING, AND PARTICIPANTS: The VIABLE double-blind, parallel-group, placebo-controlled, phase 3 randomized clinical trial enrolled patients with mCRPC among 177 hospital clinics in the US and Europe between June 2014 and November 2017. Data analyses were performed from December 2019 to July 2020. INTERVENTIONS: Eligible patients were randomized (2:1) to receive DCVAC/PCa (add-on and maintenance) or placebo, both in combination with chemotherapy (docetaxel plus prednisone). The stratification was applied according to geographical region (US or non-US), prior therapy (abiraterone, enzalutamide, or neither), and Eastern Cooperative Oncology Group performance status (0-1 or 2). DCVAC/PCa or placebo was administered subcutaneously every 3 to 4 weeks (up to 15 doses). MAIN OUTCOMES AND MEASURES: The primary outcome was overall survival (OS), defined as the time from randomization until death due to any cause, in all randomized patients. Survival was compared using 2-sided log-rank test stratified by geographical region, prior therapy with abiraterone and/or enzalutamide, and Eastern Cooperative Oncology Group performance status. RESULTS: A total of 1182 men with mCRPC (median [range] age, 68 [46-89] years) were randomized to receive DCVAC/PCa (n = 787) or placebo (n = 395). Of these, 610 (81.8%) started DCVAC/PCa, and 376 (98.4%) started placebo. There was no difference in OS between the DCVAC/PCa and placebo groups in all randomized patients (median OS, 23.9 months [95% CI, 21.6-25.3] vs 24.3 months [95% CI, 22.6-26.0]; hazard ratio, 1.04; 95% CI, 0.90-1.21; P = .60). No differences in the secondary efficacy end points (radiological progression-free survival, time to prostate-specific antigen progression, or skeletal-related events) were observed. Treatment-emergent adverse events related to DCVAC/PCa or placebo occurred in 69 of 749 (9.2%) and 48 of 379 (12.7%) patients, respectively. The most common treatment-emergent adverse events (DCVAC/PCa [n = 749] vs placebo [n = 379]) were fatigue (271 [36.2%] vs 152 [40.1%]), alopecia (222 [29.6%] vs 130 [34.3%]), and diarrhea (206 [27.5%] vs 117 [30.9%]). CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, DCVAC/PCa combined with docetaxel plus prednisone and continued as maintenance treatment did not extend OS in patients with mCRPC and was well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02111577.

Bristol Haematology and Oncology Centre Bristol United Kingdom

Center of Oncology of the Lublin Region St Jana z Dukli Lublin Poland

Comprehensive Cancer Centers of Nevada Las Vegas

CUIMED Bratislava Slovakia

Faculty of Medicine in Hradec Kralove Charles University Czechia

Georges Pompidou European Hospital University of Paris Paris France

Geza Hetenyi Hospital in Szolnok Szolnok Hungary

Instituto Português de Oncologia do Porto Francisco Gentil Porto Portugal

Minsk City Oncological Dispensary Minsk Belarus

Oncology Center Institute Marii Sklodowskiej Curie Warszawa Poland

Oncology Institute of Hope and Innovation Long Beach California

Oregon Health and Science University Portland

Radboud UMC Nijmegen the Netherlands

Regional Hospital Liberec Liberec Czechia

Royal Marsden NHS Foundation Trust Sutton United Kingdom

SOTIO a s Prague Czechia

Studienpraxis Urologie Nuertingen Germany

University Clinic of Urology Tuebingen Germany

University Hospital Medical Center Bezanijska Kosa Belgrade Serbia

University Hospital Ostrava Ostrava Czechia

University of Maryland Greenebaum Comprehensive Cancer Center Baltimore Maryland

University of Sheffield Sheffield United Kingdom

US Oncology Research The Woodlands Texas

JAMA Oncol. 2022 Apr 1;8(4):522-523. doi: 10.1001/jamaoncol.2021.7282. PubMed

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Peripheral gene signatures reveal distinct cancer patient immunotypes with therapeutic implications for autologous DC-based vaccines

Trial watch: Dendritic cell (DC)-based immunotherapy for cancer

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ClinicalTrials.gov
NCT02111577