Milada Zemanova1, Marketa Cernovska2, Libor Havel2, Tomas Bartek3, Sarka Lukesova4, Jitka Jakesova5, Jaroslav Vanasek6, Pavel Reiterer7, Juraj Kultan8, Igor Andrasina9, Lenka Siskova10, Leona Koubkova11, Jana Skrickova12, Frantisek Salajka13, Milos Pesek14, Petr Klepetko15, Juraj Beniak16, Harald Fricke17, Pavla Kadlecova17, Roman P Korolkiewicz18, Marek Hraska17, Jirina Bartunkova17, Radek Spisek17. 1. Department of Oncology, General Teaching Hospital, Prague, Czech Republic; First Faculty of Medicine, Charles University, Prague, Czech Republic. 2. First Faculty of Medicine, Charles University, Prague, Czech Republic; Department of Respiratory Medicine, Thomayer Hospital, Prague, Czech Republic. 3. Department of Respiratory Medicine and Tuberculosis, University Hospital Ostrava, Ostrava, Czech Republic. 4. Department of Oncology, Hospital Nachod, Nachod, Czech Republic. 5. Department of Oncology, Hospital Pribram, Pribram, Czech Republic. 6. Oncology Centre Multiscan, Pardubice, Czech Republic. 7. Department of Pneumology, Masaryk Hospital Usti and Labem, Usti and Labem, Czech Republic. 8. Department of Respiratory Medicine, University Hospital Olomouc, Olomouc, Czech Republic. 9. Department of Oncology, Vychodoslovensky onkologicky ustav, a.s., Kosice, Slovak Republic. 10. Department of Oncology, Hospital of Tomas Bata in Zlin, Zlin, Czech Republic. 11. Department of Pneumology, 2nd Faculty of Medicine, University Hospital Motol, Charles University, Prague, Prague, Czech Republic. 12. Department of Respiratory Medicine and Tuberculosis, University Hospital Brno, Brno, Czech Republic. 13. Department of Pneumology, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic. 14. Department of Pneumology, University Hospital Pilsen, Charles University in Prague, Prague, Czech Republic. 15. Avicennus Oncology, Kutna Hora, Czech Republic. 16. POKO Poprad, Poprad, Slovak Republic. 17. SOTIO a.s., Prague, Czech Republic. 18. SOTIO a.s., Prague, Czech Republic. Electronic address: korolkiewicz@sotio.com.
Abstract
PURPOSE: To investigate the efficacy and safety of an active cellular immunotherapy (DCVAC/LuCa) and chemotherapy in patients with stage IV non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: SLU01 was a multicenter, open-label, parallel-group, randomized, phase I/II trial. NSCLC patients were randomized in a ratio of 1:1:1 to receive: DCVAC/LuCa and chemotherapy (carboplatin and paclitaxel; Group A); DCVAC/LuCa, chemotherapy, pegylated interferon-α2b, and hydroxychloroquine (Group B); or chemotherapy alone (Group C). DCVAC/LuCa was administered subcutaneously every 3-6 weeks (up to 15 doses). The primary endpoint was overall survival (OS). During the study, enrollment into Group B was discontinued for strategic reasons. RESULTS: Forty-five patients were randomized to Group A, 29 patients to Group B, and 38 patients to Group C. The median OS in the modified intention-to-treat (mITT) population was 3.7 months longer in Group A than in Group C (15.5 vs. 11.8 months; p = 0.0179; hazard ratio = 0.54; 95% confidence interval: 0.32-0.91). This OS effect was consistent across subgroups of the mITT population (females, males, current smokers, former smokers, and patients with non-squamous and squamous cell histology). The most common treatment-emergent adverse events of any grade reported in Groups A, B, and C, respectively, were neutropenia (50.0%, 29.6%, and 20.6%), fatigue (40.0%, 18.5%, and 20.6%), anemia (35.0%, 44.4%, and 32.4%), paresthesia (27.5%, 25.9%, and 17.6%), and alopecia (25.0%, 29.6%, and 41.2%). CONCLUSION: DCVAC/LuCa in combination with carboplatin and paclitaxel extended OS and was well tolerated.
PURPOSE: To investigate the efficacy and safety of an active cellular immunotherapy (DCVAC/LuCa) and chemotherapy in patients with stage IV non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: SLU01 was a multicenter, open-label, parallel-group, randomized, phase I/II trial. NSCLC patients were randomized in a ratio of 1:1:1 to receive: DCVAC/LuCa and chemotherapy (carboplatin and paclitaxel; Group A); DCVAC/LuCa, chemotherapy, pegylated interferon-α2b, and hydroxychloroquine (Group B); or chemotherapy alone (Group C). DCVAC/LuCa was administered subcutaneously every 3-6 weeks (up to 15 doses). The primary endpoint was overall survival (OS). During the study, enrollment into Group B was discontinued for strategic reasons. RESULTS: Forty-five patients were randomized to Group A, 29 patients to Group B, and 38 patients to Group C. The median OS in the modified intention-to-treat (mITT) population was 3.7 months longer in Group A than in Group C (15.5 vs. 11.8 months; p = 0.0179; hazard ratio = 0.54; 95% confidence interval: 0.32-0.91). This OS effect was consistent across subgroups of the mITT population (females, males, current smokers, former smokers, and patients with non-squamous and squamous cell histology). The most common treatment-emergent adverse events of any grade reported in Groups A, B, and C, respectively, were neutropenia (50.0%, 29.6%, and 20.6%), fatigue (40.0%, 18.5%, and 20.6%), anemia (35.0%, 44.4%, and 32.4%), paresthesia (27.5%, 25.9%, and 17.6%), and alopecia (25.0%, 29.6%, and 41.2%). CONCLUSION: DCVAC/LuCa in combination with carboplatin and paclitaxel extended OS and was well tolerated.
Keywords:
Cellular immunotherapy; Dendritic cells and a platinum doublet; Immuno-oncology; Immunotherapy combined with platinum-based chemotherapy; Metastatic non-small cell lung cancer
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