Efficacy and Safety of Autologous Dendritic Cell–Based Immunotherapy, Docetaxel, and Prednisone vs Placebo in Patients With Metastatic Castration-Resistant Prostate Cancer
Authors: 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, Walter Stadler, Arthur S. Berg, Karl-Heinz Kurth, Celestia S. Higano, Matti Aapro, Michael Krainer, Stephan Hruby, Johannes Meran, Sergey Polyakov, Jean-Pascal Machiels, Thierry Roumeguere, Koen Ackaert, Nicolaas Lumen, Thierry Gil, Velko Minchev, Antoaneta Tomova, Borislav Dimitrov, Marchela Koleva, Antonio Juretic, Ana Fröbe, Zeljko Vojnovic, Martin Drabek, Ladislav Jarolim, Tomas Buchler, Eva Kindlova, Jan Schraml, Milada Zemanova, Jana Prausova, Bohuslav Melichar, Martina Chodacka, Jan Jansa, Gedske Daugaard, Nicolas Delonchamps, Brigitte Duclos, Stéphane Culine, Gael Deplanque, Sylvestre Le Moulec, Peter Hammerer, Gerald Rodemer, Manuel Ritter, Axel Merseburger, Marc-Oliver Grimm, Ilija Damjanoski, Manfred Wirth, Martin Burmester, Kurt Miller, Jan Herden, Bastian Keck, Christian Wuelfing, Alexander Winter, Martin Boegemann, Ingo Kausch von Schmeling, Paolo Fornara, Elke Jaeger, György Bodoky, Zsuzsanna Pápai, Géza Böszörményi-Nagy, Paola Vanella, Hector SotoParra, Rodolfo Passalacqua, Francesco Ferrau, Michele Maio, Lucia Fratino, Enrico Cortesi, Gunta Purkalne, Jolita Asadauskiene, Rasa Janciauskiene, Skaiste Tulyte, Alvydas Cesas, Marco Polee, Brigitte Haberkorn, Fons van de Eertwegh, Pieter van den Berg, Aart Beeker, Peter Nieboer, Romuald Zdrojowy, Elzbieta Staroslawska, Jacek Fijuth, Bozena Sikora-Kupis, Boguslawa Karaszewska, Isabel Fernandes, Gabriela Sousa, Tânia Rodrigues, Zoran Dzamic, Nada Babovic, Bora Cvetkovic, Roman Sokol, Juraj Mikuláš, Milan Gajdos, Marek Brezovsky, Ivan Mincik, Jan Breza, Jose Angel Arranz, Virginia Calvo, Gustavo Rubio, Manuel Sanchez Chapado, Pablo Gajete Boreu, Alvaro Montesa, David Olmos, Begona Mellado, Daniel Castellano, Javier Puente, Erika Thellenberg Karlsson, Johan Ahlgren, Hardev Pandha, Danish Mazhar, Maria Vilarino-Varela, Tony Elliott, Ian Pedley, Anjali Zarkar, Amy Law, Dennis Slater, Gary Karlin, Marijo Bilusic, Charles Redfern, Rakesh Gaur, Robert McCroskey, David Clarkson, Manish Agrawal, Mikhail Shtivelband, Luke Nordquist, Nagla Karim, Ralph Hauke, Thomas Flaig, Haresh Jhangiani, Rakesh Singal, Brian Choi, Evangeline Reyes, John Corman, Clara Hwang, Leonard Appleman, Edward McClay, Mark Fleming, Vijay Gunuganti, Eric Cheung, Benjamin Gartrell, Alton Sartor, Stephen Williamson, Jitendra Gandhi, Ian Schnadig, John Burke, Stuart Bloom, Neal Shore, Tina Mayer, William Oh, Alan Bryce, Laurence Belkoff, Ulka Vaishampayan, Sanjiv Agarwala, Omer Kucuk, Apurv Agrawal, William Walsh, Bernard Poiesz, Lauren Harshman, Nancy Dawson, Sanjay Sharma
Journal: JAMA Oncology (2022)

<h3>Importance</h3> DCVAC/PCa is an active cellular immunotherapy designed to initiate an immune response against prostate cancer. <h3>Objective</h3> 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). <h3>Design, Setting, and Participants</h3> 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. <h3>Interventions</h3> 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). <h3>Main Outcomes and Measures</h3> 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. <h3>Results</h3> 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;<i>P</i> = .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%]). <h3>Conclusions and Relevance</h3> 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. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02111577