DCVAC/PCa is an active cellular immunotherapy designed to initiate an immune response against prostate cancer.
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).
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.
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).
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.
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%]).
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.
ClinicalTrials.gov Identifier: NCT02111577.
JAMA oncology. 2022 Feb 10 [Epub ahead of print]
Nicholas J Vogelzang, Tomasz M Beer, Winald Gerritsen, Stéphane Oudard, Pawel Wiechno, Bozena Kukielka-Budny, Vladimir Samal, Jaroslav Hajek, Susan Feyerabend, Vincent Khoo, Arnulf Stenzl, Tibor Csöszi, Zoran Filipovic, Frederico Goncalves, Alexander Prokhorov, Eric Cheung, Arif Hussain, Nuno Sousa, Amit Bahl, Syed Hussain, Harald Fricke, Pavla Kadlecova, Tomas Scheiner, Roman P Korolkiewicz, Jirina Bartunkova, Radek Spisek, VIABLE Investigators
Comprehensive Cancer Centers of Nevada, Las Vegas., Oregon Health & Science University, Portland., Radboud UMC, Nijmegen, the Netherlands., Georges Pompidou European Hospital, University of Paris, Paris, France., Oncology Center-Institute Marii Sklodowskiej-Curie, Warszawa, Poland., Center of Oncology of the Lublin Region St Jana z Dukli, Lublin, Poland., Regional Hospital Liberec, Liberec, Czechia., University Hospital Ostrava, Ostrava, Czechia., Studienpraxis Urologie, Nuertingen, Germany., Royal Marsden NHS Foundation Trust, Sutton, United Kingdom., University Clinic of Urology, Tuebingen, Germany., Geza Hetenyi Hospital in Szolnok, Szolnok, Hungary., University Hospital Medical Center Bezanijska Kosa, Belgrade, Serbia., CUIMED, Bratislava, Slovakia., Minsk City Oncological Dispensary, Minsk, Belarus., Oncology Institute of Hope and Innovation, Long Beach, California., University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, Maryland., Instituto Português de Oncologia do Porto Francisco Gentil, Porto, Portugal., Bristol Haematology and Oncology Centre, Bristol, United Kingdom., University of Sheffield, Sheffield, United Kingdom., SOTIO a.s., Prague, Czechia.