First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743

S Peters; A Scherpereel; R Cornelissen; Y Oulkhouir; L Greillier; M A Kaplan; T Talbot; I Monnet; S Hiret; P Baas; A K Nowak; N Fujimoto; A S Tsao; A S Mansfield; S Popat; X Zhang; N Hu; D Balli; T Spires; G Zalcman

doi:10.1016/j.annonc.2022.01.074

First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743

Ann Oncol. 2022 May;33(5):488-499. doi: 10.1016/j.annonc.2022.01.074. Epub 2022 Feb 3.

Authors

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

Affiliations

¹ Oncology Department, Lausanne University Hospital, Lausanne, Switzerland. Electronic address: [email protected].
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.

PMID: 35124183
DOI: 10.1016/j.annonc.2022.01.074

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.

Keywords: CTLA-4; PD-L1; dual immunotherapy; first-line; immune checkpoint inhibitors; overall survival.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Humans
Ipilimumab / adverse effects
Mesothelioma, Malignant*
Nivolumab* / therapeutic use
Progression-Free Survival

Substances

Ipilimumab
Nivolumab

Associated data

ClinicalTrials.gov/NCT02899299