{"doi":"10.1016/j.annonc.2022.01.074","title":"First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743","abstract":"•With a ≥3-year follow-up in CheckMate 743, nivolumab + ipilimumab continued to provide long-term OS benefit in first-line MPM.•Clinical benefits remained consistent across patient subgroups, including epithelioid versus non-epithelioid histology.•Discontinuing nivolumab + ipilimumab due to TRAEs did not negatively impact long-term benefit.•Nivolumab + ipilimumab continues to be an efficacious first-line treatment option for patients with unresectable MPM. BackgroundIn 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 methodsAdults 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).ResultsWith 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.ConclusionsWith 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. 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. 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). 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","journal":"Annals of Oncology","year":2022,"id":232105,"datarank":5.6561517626854565,"base_score":5.583496308781699,"endowment":5.583496308781699,"self_citation_contribution":0.837524446317255,"citation_network_contribution":4.818627316368201,"self_endowment_contribution":0.837524446317255,"citer_contribution":4.818627316368201,"corpus_percentile":null,"corpus_rank":null,"citation_count":265,"citer_count":100,"citers_with_citation_signal":100,"citers_with_endowment":100,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9401,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02899299"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":839097,"name":"Arnaud Scherpereel","orcid":"0000-0002-7607-1863","position":1,"is_corresponding":false},{"id":841569,"name":"Robin Cornelissen","orcid":"0000-0002-4289-3092","position":2,"is_corresponding":false},{"id":842904,"name":"Youssef Oulkhouir","orcid":null,"position":3,"is_corresponding":false},{"id":841570,"name":"Laurent Greillier","orcid":"0000-0002-5807-9503","position":4,"is_corresponding":false},{"id":841571,"name":"Kaplan Ma","orcid":"0000-0003-0882-0524","position":5,"is_corresponding":false},{"id":841572,"name":"Thomas Talbot","orcid":"0000-0002-4658-4115","position":6,"is_corresponding":false},{"id":841573,"name":"I. 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Zhang","orcid":"0000-0002-8380-8667","position":15,"is_corresponding":false},{"id":841577,"name":"Nan Hu","orcid":"0000-0002-0304-766X","position":16,"is_corresponding":false},{"id":6503,"name":"David Balli","orcid":"0000-0002-3007-4495","position":17,"is_corresponding":false},{"id":244323,"name":"Thomas Spires","orcid":null,"position":18,"is_corresponding":false},{"id":91582,"name":"Gérard Zalcman","orcid":"0000-0002-0343-9575","position":19,"is_corresponding":false},{"id":90049,"name":"Solange Peters","orcid":"0000-0002-0412-7143","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T00:21:12.348693Z","pmid":"35124183","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}