S Peters1, A Scherpereel2, R Cornelissen3, Y Oulkhouir4, L Greillier5, M A Kaplan6, T Talbot7, I Monnet8, S Hiret9, P Baas10, A K Nowak11, N Fujimoto12, A S Tsao13, A S Mansfield14, S Popat15, X Zhang16, N Hu17, D Balli18, T Spires19, G Zalcman20. 1. Oncology Department, Lausanne University Hospital, Lausanne, Switzerland. Electronic address: solange.peters@chuv.ch. 2. Pulmonary and Thoracic Oncology, University of Lille, CHU Lille, INSERM U1189, OncoThAI, Lille, France. 3. Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. 4. Pulmonary and Thoracic Oncology Department, Hôpital Côte de Nacre C H U Caen, Caen, France. 5. Aix Marseille University, APHM, INSERM, CNRS, CRCM, Hôpital Nord, Multidisciplinary Oncology and Therapeutic Innovations Department, Marseille, France. 6. Medical Oncology, Medical School, Dicle University, Diyarbakir, Turkey. 7. The Sunrise Centre, Royal Cornwall Hospitals NHS Trust, Truro, UK. 8. Department of Pulmonology, Centre Hospitalier Intercommunal de Créteil, Créteil, France. 9. Medical Oncology, Institut de Cancérologie de l'Ouest, Site René Gauducheau, Boulevard Jacques Monod, Saint-Herblain Cedex, France. 10. Department of Thoracic Oncology, Netherlands Cancer Institute and Leiden University Medical Center, Amsterdam, The Netherlands. 11. Medical School, University of Western Australia and Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, Australia. 12. Department of Medical Oncology, Okayama Rosai Hospital, Okayama, Japan. 13. Department of Thoracic/Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, USA. 14. Division of Medical Oncology, Mayo Clinic, Rochester, USA. 15. Lung Unit, Royal Marsden Hospital, London, UK; Institute of Cancer Research, London, UK. 16. Oncology Clinical Development, Bristol Myers Squibb, Princeton, USA. 17. Biostatistics, Bristol Myers Squibb, Princeton, USA. 18. Translational Medicine, Bristol Myers Squibb, Princeton, USA. 19. Department of Informatics and Predictive Sciences, Bristol Myers Squibb, Princeton, USA. 20. Thoracic Oncology Department, Early Phases Unit-CIC INSERM 1425-CLIP2 Paris Nord, Bichat-Claude Bernard Hospital, AP-HP, University Cancer Institute Paris, Paris, France.
Abstract
BACKGROUND: In the phase III CheckMate 743 study (NCT02899299), first-line nivolumab plus ipilimumab significantly improved overall survival (OS) versus chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM). We report updated data with 3-year minimum follow-up. PATIENTS AND METHODS: Adults with previously untreated, histologically confirmed, unresectable MPM and Eastern Cooperative Oncology Group performance status of ≤1 were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks) for up to 2 years, or six cycles of platinum plus pemetrexed chemotherapy. This report includes updated efficacy and safety outcomes, exploratory biomarker analyses including four-gene inflammatory expression signature score, and a post hoc efficacy analysis in patients who discontinued treatment due to treatment-related adverse events (TRAEs). RESULTS: With a median follow-up of 43.1 months, nivolumab plus ipilimumab continued to prolong OS versus chemotherapy. Median OS was 18.1 versus 14.1 months [hazard ratio (95% confidence interval), 0.73 (0.61-0.87)], and 3-year OS rates were 23% versus 15%, respectively. Three-year progression-free survival rates were 14% versus 1%, and objective response rates were 40% versus 44%. At 3 years, 28% versus 0% of responders had an ongoing response. Improved survival benefit with nivolumab plus ipilimumab versus chemotherapy was observed across subgroups, including histology. A high score of the four-gene inflammatory signature appeared to correlate with improved survival benefit with nivolumab plus ipilimumab. No new safety signals were observed with nivolumab plus ipilimumab, despite patients being off therapy for 1 year. In patients who discontinued nivolumab plus ipilimumab due to TRAEs, median OS was 25.4 months, and 34% of responders maintained their responses for ≥3 years after discontinuation. CONCLUSIONS: With 3 years' minimum follow-up, nivolumab plus ipilimumab continued to provide long-term survival benefit over chemotherapy and a manageable safety profile, supporting the regimen as standard-of-care treatment for unresectable MPM, regardless of histology.
BACKGROUND: In the phase III CheckMate 743 study (NCT02899299), first-line nivolumab plus ipilimumab significantly improved overall survival (OS) versus chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM). We report updated data with 3-year minimum follow-up. PATIENTS AND METHODS: Adults with previously untreated, histologically confirmed, unresectable MPM and Eastern Cooperative Oncology Group performance status of ≤1 were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks) for up to 2 years, or six cycles of platinum plus pemetrexed chemotherapy. This report includes updated efficacy and safety outcomes, exploratory biomarker analyses including four-gene inflammatory expression signature score, and a post hoc efficacy analysis in patients who discontinued treatment due to treatment-related adverse events (TRAEs). RESULTS: With a median follow-up of 43.1 months, nivolumab plus ipilimumab continued to prolong OS versus chemotherapy. Median OS was 18.1 versus 14.1 months [hazard ratio (95% confidence interval), 0.73 (0.61-0.87)], and 3-year OS rates were 23% versus 15%, respectively. Three-year progression-free survival rates were 14% versus 1%, and objective response rates were 40% versus 44%. At 3 years, 28% versus 0% of responders had an ongoing response. Improved survival benefit with nivolumab plus ipilimumab versus chemotherapy was observed across subgroups, including histology. A high score of the four-gene inflammatory signature appeared to correlate with improved survival benefit with nivolumab plus ipilimumab. No new safety signals were observed with nivolumab plus ipilimumab, despite patients being off therapy for 1 year. In patients who discontinued nivolumab plus ipilimumab due to TRAEs, median OS was 25.4 months, and 34% of responders maintained their responses for ≥3 years after discontinuation. CONCLUSIONS: With 3 years' minimum follow-up, nivolumab plus ipilimumab continued to provide long-term survival benefit over chemotherapy and a manageable safety profile, supporting the regimen as standard-of-care treatment for unresectable MPM, regardless of histology.
Authors: Ramaswamy Govindan; Charu Aggarwal; Scott J Antonia; Marianne Davies; Steven M Dubinett; Andrea Ferris; Patrick M Forde; Edward B Garon; Sarah B Goldberg; Raffit Hassan; Matthew D Hellmann; Fred R Hirsch; Melissa L Johnson; Shakun Malik; Daniel Morgensztern; Joel W Neal; Jyoti D Patel; David L Rimm; Sarah Sagorsky; Lawrence H Schwartz; Boris Sepesi; Roy S Herbst Journal: J Immunother Cancer Date: 2022-05 Impact factor: 12.469