Five-Year Clinical Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Unresectable Pleural Mesothelioma in CheckMate 743

Our plain-English summary of Five-Year Clinical Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Unresectable Pleural Mesothelioma in CheckMate 743, by A. Scherpereel, P. Baas, A.K. Nowak, et al (Journal of Clinical Oncology, 2026).

The study

• Authors: A. Scherpereel, P. Baas, A.K. Nowak, A.S. Tsao, N. Fujimoto, S. Peters, A.S. Mansfield, S. Popat, Y. Bautista Aragon, T. Talbot, F. Grossi, D. Kowalski, M.A. Kaplan, A.F. Cardona, R. Soomro, N. Hu, A. Lee, V. Ip, Y.H. Hung, G. Zalcman
• Journal: Journal of Clinical Oncology
• Published: 2026;44(9):742-749
• Type of article: Randomized trial
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

In this 5-year follow-up from the CheckMate 743 study in patients with unresectable pleural mesothelioma (PM), we evaluated updated efficacy and safety outcomes and biomarkers and performed treatment-switching analyses with first-line nivolumab plus ipilimumab versus chemotherapy. With a median follow-up of 66.8 months, nivolumab plus ipilimumab demonstrated continued overall survival (OS) benefit versus chemotherapy in all randomly assigned patients (5-year OS rates, 14% v 6%; hazard ratio [HR], 0.74 [95% CI, 0.62 to 0.88]); similar benefit was observed regardless of tumor histology. Of biomarker-evaluable patients treated with nivolumab plus ipilimumab (n = 242), high baseline monocytic myeloid-derived suppressor cell (M-MDSC) levels correlated with worse OS versus low M-MDSC levels (HR, 1.25 [95% CI, 1.09 to 1.43]). After adjusting for 24% of patients in the chemotherapy arm who received subsequent immunotherapy, nivolumab plus ipilimumab demonstrated continued OS benefit versus chemotherapy (HR, 0.64 [95% CI, 0.53 to 0.78]). No new safety signals were observed. These results demonstrate long-term, durable clinical benefit with nivolumab plus ipilimumab versus chemotherapy, which continued to be preserved even after treatment-switching adjustment in the chemotherapy arm. Exploratory analyses suggested greater benefit with nivolumab plus ipilimumab in the low M-MDSC subgroup. These results further support first-line nivolumab plus ipilimumab as standard of care for unresectable PM.

In plain English

This was a five-year update of CheckMate 743, a randomized phase III trial in people with unresectable pleural mesothelioma (cancer that could not be removed surgically). Of 605 patients, 303 were assigned to nivolumab plus ipilimumab (two immunotherapy drugs) and 302 to platinum-pemetrexed chemotherapy. The article did not study asbestos exposure. After a median follow-up of 66.8 months, five-year survival was 14% with nivolumab plus ipilimumab versus 6% with chemotherapy (hazard ratio 0.74, 95% CI 0.62 to 0.88). It was 14% versus 8% for epithelioid tumors (HR 0.85, 95% CI 0.69 to 1.03) and 12% versus 1% for nonepithelioid tumors (HR 0.48, 95% CI 0.33 to 0.68). After adjusting for the 24% of chemotherapy patients who later received immunotherapy, the hazard ratio was 0.64 (95% CI 0.53 to 0.78). In an exploratory analysis of 242 immunotherapy patients, higher blood levels of M-MDSC cells were associated with worse survival. No new safety signals were found. The authors concluded the benefit was long-term and durable regardless of tumor histology, and that prospective studies are needed to confirm the M-MDSC findings.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Five-year follow-up report of a randomized phase III clinical trial (CheckMate 743) comparing two first-line treatments, with exploratory biomarker and treatment-switching analyses
• Who was studied: 605 patients with unresectable pleural mesothelioma: 303 randomly assigned to nivolumab plus ipilimumab and 302 to chemotherapy. Most were from Europe (58% in each arm), and about three-quarters had epithelioid tumors. The database was locked June 14, 2023. Enrollment dates were not given in this text.
• Exposure: The treatments compared, not an asbestos exposure: nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks, versus cisplatin or carboplatin plus pemetrexed every 3 weeks for at most six cycles. No asbestos or fiber exposure data are reported.
• Main results:
  • All randomly assigned patients: overall survival hazard ratio 0.74 (95% CI 0.62 to 0.88) for nivolumab plus ipilimumab versus chemotherapy. Five-year overall survival was 14% versus 6%, and median overall survival was 18.1 versus 14.1 months.
  • Epithelioid pleural mesothelioma: five-year overall survival 14% versus 8% (HR 0.85, 95% CI 0.69 to 1.03). Nonepithelioid pleural mesothelioma: 12% versus 1% (HR 0.48, 95% CI 0.33 to 0.68).
  • Progression-free survival in all randomly assigned patients: HR 0.93 (95% CI 0.77 to 1.13). The five-year progression-free survival rate was 8% with nivolumab plus ipilimumab; all chemotherapy patients had been censored or had a progression event before 5 years.
  • Objective response rates were 39% with nivolumab plus ipilimumab and 44% with chemotherapy. At 5 years, 17% of responders on nivolumab plus ipilimumab and 0% of responders on chemotherapy had an ongoing response.
  • Among M-MDSC-evaluable patients treated with nivolumab plus ipilimumab (242 patients), higher blood M-MDSC levels were associated with worse overall survival (HR 1.25, 95% CI 1.09 to 1.43) and worse progression-free survival (HR 1.23, 95% CI 1.06 to 1.44). These hazard ratios are per 1-unit increase in log-transformed M-MDSC level.
  • 72 (24%) chemotherapy-arm patients received later immunotherapy. After adjusting for this (IPCW method), median overall survival with chemotherapy was 12.1 months and the hazard ratio for nivolumab plus ipilimumab versus chemotherapy was 0.64 (95% CI 0.53 to 0.78).
  • No new safety signals were identified.
• The authors' conclusion: The authors concluded that the 5-year update showed continued long-term, durable clinical benefit of first-line nivolumab plus ipilimumab in pleural mesothelioma regardless of tumor histology. They wrote that the results further support it as standard of care for unresectable pleural mesothelioma.
• Limitations the authors state:
  • The M-MDSC biomarker analyses were exploratory, and the authors state that further prospective studies are needed to confirm the link between M-MDSC levels and outcomes.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Nivolumab (Opdivo), Ipilimumab (Yervoy), Chemotherapy, Unresectable Pleural Mesothelioma, CheckMate 743, Biomarker, Overall Survival, Hazard Ratio.

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