PMID- 37285717 OWN - NLM STAT- MEDLINE DCOM- 20230703 LR - 20231116 IS - 2059-7029 (Electronic) IS - 2059-7029 (Linking) VI - 8 IP - 3 DP - 2023 Jun TI - Efficacy and safety of nivolumab for patients with pre-treated type B3 thymoma and thymic carcinoma: results from the EORTC-ETOP NIVOTHYM phase II trial. PG - 101576 LID - S2059-7029(23)00808-6 [pii] LID - 10.1016/j.esmoop.2023.101576 [doi] LID - 101576 AB - BACKGROUND: Thymic malignancies are rare intrathoracic tumors, which may be aggressive and difficult to treat. They represent a therapeutic challenge in the advanced/metastatic setting, with limited treatment options after the failure of first-line platinum-based chemotherapy. They are frequently associated with autoimmune disorders that also impact oncological management. MATERIALS AND METHODS: NIVOTHYM is an international, multicenter, phase II, two-cohort, single-arm trial evaluating the activity and safety of nivolumab [240 mg intravenously (i.v.) q2 weeks] alone or with ipilimumab (1 mg /kg i.v. q6 weeks) in patients with advanced/relapsed type B3 thymoma or thymic carcinoma, after exposure to platinum-based chemotherapy. The primary endpoint is progression-free survival rate at 6 months (PFSR-6) based on RECIST 1.1 as per independent radiological review. RESULTS: From April 2018 to February 2020, 55 patients were enrolled in 15 centers from 5 countries. Ten patients (18%) had type B3 thymoma and 43 (78%) had thymic carcinoma. The majority were male (64%), and the median age was 58 years. Among the 49 eligible patients who started treatment, PFSR-6 by central review was 35% [95% confidence interval (CI) 22% to 50%]. The overall response rate and disease control rate were 12% (95% CI 5% to 25%) and 63% (95% CI 48% to 77%), respectively. Using the Kaplan-Meier method, median progression-free survival and overall survival by local assessment were 6.0 (95% CI 3.1-10.4) months and 21.3 (95% CI 11.6-not estimable) months, respectively. In the safety population of 54 patients, adverse events (AEs) of grade 1/2 were observed in 22 (41%) patients and grade 3/4 in 31 (57%) patients. Treatment-related AEs of grade 4 included one case of neutropenia, one case of immune-mediated transaminitis, and two cases of myocarditis. CONCLUSIONS: Nivolumab monotherapy demonstrated an acceptable safety profile and objective activity, although it has been insufficient to meet its primary objective. The second cohort of NIVOTHYM is currently ongoing to assess the combination of nivolumab plus ipilimumab. CI - Crown Copyright (c) 2023. Published by Elsevier Ltd. All rights reserved. FAU - Girard, N AU - Girard N AD - Thorax Institute Curie Montsouris, Institut Curie, Paris, France and Paris Saclay University, UVSQ, Versailles, France. Electronic address: nicolas.girard2@curie.fr. FAU - Ponce Aix, S AU - Ponce Aix S AD - Hospital Universitario 12 De Octubre, Madrid, Spain. FAU - Cedres, S AU - Cedres S AD - Hospital Universitari Vall d'Hebron-Vall d'Hebron Institut Oncologia, Barcelona, Spain. FAU - Berghmans, T AU - Berghmans T AD - Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium. FAU - Burgers, S AU - Burgers S AD - The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis, Amsterdam, The Netherlands. FAU - Toffart, A-C AU - Toffart AC AD - CHU de Grenoble-La Tronche-Hopital A. Michallon, Grenoble, France. FAU - Popat, S AU - Popat S AD - Royal Marsden Hospital-Chelsea, London, UK. FAU - Janssens, A AU - Janssens A AD - Universitair Ziekenhuis Antwerpen, Antwerp, Belgium. FAU - Gervais, R AU - Gervais R AD - Centre Francois Baclesse (CLCC), Caen, France. FAU - Hochstenbag, M AU - Hochstenbag M AD - Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands. FAU - Silva, M AU - Silva M AD - Department of Medicine and Surgery (DiMeC), University of Parma, Parma, Italy. FAU - Burger, I A AU - Burger IA AD - Kantonsspital Baden, Baden, Switzerland. FAU - Prosch, H AU - Prosch H AD - Medical University of Vienna, Vienna, Austria. FAU - Stahel, R AU - Stahel R AD - ETOP IBCSG Partners Foundation, Berne, Switzerland. FAU - Xenophontos, E AU - Xenophontos E AD - EORTC Headquarters, Brussels, Belgium. FAU - Pretzenbaher, Y AU - Pretzenbaher Y AD - EORTC Headquarters, Brussels, Belgium. FAU - Neven, A AU - Neven A AD - Luxembourg Institute of Health, Competence Center for Methodology and Statistics, Strassen, Luxembourg. FAU - Peters, S AU - Peters S AD - Centre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne, Switzerland. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study DEP - 20230606 PL - England TA - ESMO Open JT - ESMO open JID - 101690685 RN - 31YO63LBSN (Nivolumab) RN - 0 (Ipilimumab) SB - IM MH - Humans MH - Male MH - Female MH - Middle Aged MH - Nivolumab/adverse effects MH - Ipilimumab/adverse effects MH - *Thymoma/drug therapy/chemically induced MH - *Thymus Neoplasms/drug therapy/chemically induced MH - Progression-Free Survival PMC - PMC10265606 OTO - NOTNLM OT - immunotherapy OT - thymic carcinoma OT - thymoma COIS- Disclosure EX: all support for the present manuscript: medical writing, data analysis. SP: consulting fees from Amgen, AstraZeneca, Bayer, Beigene, Blueprint, BMS, Boehringer, Ingelheim, Daiichi Sankyo, Guardant Health, Incyte, Janssen, Lilly, Merck Serono, MSD, Novartis, Roche, Takeda, Pfizer, Seattle Genetics, Turning Point Therapeutics, EQRx. Payment or honoraria from: AstraZeneca, Bayer, Guardant Health, Janssen, Merck Serono, Roche, Takeda, Pfizer. Payment for expert testimony from Roche, Merck Serono. Support for attending meetings and/or travel from Janssen, Roche. Advisory Board as per consulting fees. Leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid: British Thoracic Oncology Group, ALK Positive UK, Lung Cancer Europe, Ruth Strauss Foundation, Mesothelioma Applied Research Foundation, ETOP-IBCSG Partners Foundation Board. SC: payment or honoraria from BMS. Participation on a Data Safety Monitoring Board or Advisory Board from BMS. TB: Advisory Board for Bayer, Janssen, and Roche. ACT: grants, personal fees, and non-financial support from Roche, personal fees and non-financial support from Astra Zeneca, personal fees and non-financial support from MSD, grants, personal fees and non-financial support from BMS, during the conduct of the study; personal fees and non-financial support from Novartis, personal fees and non-financial support from Vifor Pharma, personal fees from Boehringer Ingelheim, grants, personal fees, and non-financial support from Pfizer, personal fees and non-financial support from Amgen, personal fees and non-financial support from Takeda, outside the submitted work. SP: support for the present manuscript from Astra Zeneca, funding to institution to support study conduct; medical writing support (no direct transfer of funds). Principal investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Beigene, Bristol-Myers Squibb, GSK, Merck Sharp and Dohme, Roche/Genentech. All fees to institution. Consulting fees from: AbbVie, AiCME, Amgen, Arcus, AstraZeneca, Bayer, Beigene, Biocartis, BioInvent, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, F-Star, Fishawack, Foundation Medicine, Genzyme, Gilead, GSK, Illumina, Imedex, IQVIA, Incyte, Ipsen, iTeos, Janssen, Medscape, Medtoday, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, Novocure, OncologyEducation, Pharma Mar, Phosplatin Therapeutics, PER, Peerview, Pfizer, PRIME, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seattle Genetics, Takeda, Vaccibody. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events: AiCME, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, ecancer, Eli Lilly, Foundation Medicine, Illumina, Imedex, Medscape, Merck Sharp and Dohme, Mirati, Novartis, Peerview, PER, Pfizer, Prime, Roche/Genentech, RTP, Sanofi, Takeda. Support for attending meetings and/or travel: AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer, Roche/Genentech, Takeda. Participation on a Data Safety Monitoring Board or Advisory Board: AbbVie, Amgen, Arcus, AstraZeneca, Bayer, Beigene, Biocartis, BioInvent, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F-Star, Foundation Medicine, Genzyme, Gilead, GSK, Illumina, Incyte, iTeos, Janssen, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, Novocure, Pharma Mar, Phosplatin Therapeutics, Pfizer, Regeneron, Roche/Genentech, Sanofi, Seattle Genetics, Takeda, Vaccibody. HP: grants or contracts from Boehringer Ingelheim, Astra Zeneca, Siemens, European Commission (EU4Health). Payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing or educational events: Boehringer Ingelheim, Astra Zeneca, MSD, BMS, Roche, Janssen, Sanofi. Support for attending meetings and/or travel from Boehringer Ingelheim. Leadership or fiduciary role in EFSUMB, Austrian Society of Roentgenology. Receipt of equipment, materials, drugs, medical writing, gifts, or other services from Boehringer Ingelheim. GR: all support for the present manuscript-provision of study materials. Support for attending meetings and/or travel from Roche, Astra Zeneca, MSD, BMS. Participation on a Data Safety Monitoring Board or Advisory Board from MSD. NG: grants or contracts from Astrazeneca, Janssen, MSD, BMS. Consulting fees from Astrazeneca, Roche, Bristol Myers Squibb, Merck Sharp & Dohme. Payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from Astrazeneca, Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pfizer. Payment for expert testimony from Astrazeneca. Participation on Roche Data Safety Monitoring Board. AJ: support for attending meetings and/or travel from Roche ESMO 2022. YP: employee of EORTC. All other authors have declared no conflicts of interest. EDAT- 2023/06/08 01:08 MHDA- 2023/07/03 06:41 PMCR- 2023/06/06 CRDT- 2023/06/07 18:05 PHST- 2023/02/03 00:00 [received] PHST- 2023/04/07 00:00 [revised] PHST- 2023/04/24 00:00 [accepted] PHST- 2023/07/03 06:41 [medline] PHST- 2023/06/08 01:08 [pubmed] PHST- 2023/06/07 18:05 [entrez] PHST- 2023/06/06 00:00 [pmc-release] AID - S2059-7029(23)00808-6 [pii] AID - 101576 [pii] AID - 10.1016/j.esmoop.2023.101576 [doi] PST - ppublish SO - ESMO Open. 2023 Jun;8(3):101576. doi: 10.1016/j.esmoop.2023.101576. Epub 2023 Jun 6.