Nicholas J Vogelzang1,2, Tomasz M Beer3, Winald Gerritsen4, Stéphane Oudard5, Pawel Wiechno6, Bozena Kukielka-Budny7, Vladimir Samal8,9, Jaroslav Hajek10, Susan Feyerabend11, Vincent Khoo12, Arnulf Stenzl13, Tibor Csöszi14, Zoran Filipovic15, Frederico Goncalves16, Alexander Prokhorov17, Eric Cheung18, Arif Hussain19, Nuno Sousa20, Amit Bahl21, Syed Hussain22, Harald Fricke23, Pavla Kadlecova23, Tomas Scheiner23, Roman P Korolkiewicz23, Jirina Bartunkova23, Radek Spisek23. 1. Comprehensive Cancer Centers of Nevada, Las Vegas. 2. US Oncology Research, The Woodlands, Texas. 3. Oregon Health & Science University, Portland. 4. Radboud UMC, Nijmegen, the Netherlands. 5. Georges Pompidou European Hospital, University of Paris, Paris, France. 6. Oncology Center-Institute Marii Sklodowskiej-Curie, Warszawa, Poland. 7. Center of Oncology of the Lublin Region St Jana z Dukli, Lublin, Poland. 8. Regional Hospital Liberec, Liberec, Czechia. 9. Faculty of Medicine in Hradec Kralove, Charles University, Czechia. 10. University Hospital Ostrava, Ostrava, Czechia. 11. Studienpraxis Urologie, Nuertingen, Germany. 12. Royal Marsden NHS Foundation Trust, Sutton, United Kingdom. 13. University Clinic of Urology, Tuebingen, Germany. 14. Geza Hetenyi Hospital in Szolnok, Szolnok, Hungary. 15. University Hospital Medical Center Bezanijska Kosa, Belgrade, Serbia. 16. CUIMED, Bratislava, Slovakia. 17. Minsk City Oncological Dispensary, Minsk, Belarus. 18. Oncology Institute of Hope and Innovation, Long Beach, California. 19. University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, Maryland. 20. Instituto Português de Oncologia do Porto Francisco Gentil, Porto, Portugal. 21. Bristol Haematology and Oncology Centre, Bristol, United Kingdom. 22. University of Sheffield, Sheffield, United Kingdom. 23. SOTIO a.s., Prague, Czechia.
Abstract
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.
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.
Authors: Raquel S Laureano; Jenny Sprooten; Isaure Vanmeerbeerk; Daniel M Borras; Jannes Govaerts; Stefan Naulaerts; Zwi N Berneman; Benoit Beuselinck; Kalijn F Bol; Jannie Borst; An Coosemans; Angeliki Datsi; Jitka Fučíková; Lisa Kinget; Bart Neyns; Gerty Schreibelt; Evelien Smits; Rüdiger V Sorg; Radek Spisek; Kris Thielemans; Sandra Tuyaerts; Steven De Vleeschouwer; I Jolanda M de Vries; Yanling Xiao; Abhishek D Garg Journal: Oncoimmunology Date: 2022-07-04 Impact factor: 7.723
Authors: Michal Hensler; Jana Rakova; Lenka Kasikova; Tereza Lanickova; Josef Pasulka; Peter Holicek; Marek Hraska; Tereza Hrnciarova; Pavla Kadlecova; Andreu Schoenenberger; Klara Sochorova; Daniela Rozkova; Ludek Sojka; Jana Drozenova; Jan Laco; Rudolf Horvath; Michal Podrazil; Guo Hongyan; Tomas Brtnicky; Michal J Halaska; Lukas Rob; Ales Ryska; An Coosemans; Ignace Vergote; Abhishek D Garg; David Cibula; Jirina Bartunkova; Radek Spisek; Jitka Fucikova Journal: Oncoimmunology Date: 2022-07-22 Impact factor: 7.723