Five years of follow-up data from the CheckMate-743 trial confirm that nivolumab plus ipilimumab provides a durable survival advantage over chemotherapy for people with unresectable pleural mesothelioma. The results, published today in the Journal of Clinical Oncology, show that 14% of people treated with the immunotherapy combination were alive at five years, compared to 6% of those treated with chemotherapy.
The updated analysis, based on a median follow-up of 66.8 months across 605 patients, reinforces the original trial findings that led to FDA approval in October 2020.
Five-Year Survival Data
| Outcome | Immunotherapy | Chemotherapy |
|---|---|---|
| Five-year overall survival | 14% | 6% |
| Five-year progression-free survival | 8% | 0% |
| Objective response rate | 39% | 44% |
| Ongoing responses at five years | 17% | 0% |
The hazard ratio for overall survival was 0.74 (95% CI, 0.62 to 0.88), consistent with the 26% relative reduction in death risk reported in earlier analyses. Notably, none of the people who responded to chemotherapy still had ongoing responses at five years, while 17% of immunotherapy responders did.
Non-Epithelioid Results Are Striking
The most compelling finding continues to be in non-epithelioid mesothelioma (sarcomatoid and biphasic subtypes), where chemotherapy has historically offered limited benefit.
| Subtype | Immunotherapy 5-Year OS | Chemotherapy 5-Year OS | Hazard Ratio |
|---|---|---|---|
| Epithelioid | 14% | 8% | 0.85 |
| Non-epithelioid | 12% | 1% | 0.48 |
For people with non-epithelioid disease, the immunotherapy combination reduced the risk of death by 52% compared to chemotherapy. At five years, 12% of these patients were alive, versus just 1% on chemotherapy.
Non-epithelioid mesothelioma accounts for roughly 20% to 25% of cases and historically carries a worse prognosis. The CheckMate-743 five-year data suggests immunotherapy has fundamentally changed outcomes for this subgroup.
Crossover and Adjusted Analysis
Approximately 24% of people in the chemotherapy arm received subsequent immunotherapy after disease progression, compared to 6% who crossed over in the immunotherapy arm. When adjusted for this treatment switching, the chemotherapy arm’s median overall survival drops from 14.1 months to 12.1 months, and the adjusted hazard ratio improves to 0.64 (95% CI, 0.53 to 0.78).
Biomarker Findings
The study also evaluated monocytic myeloid-derived suppressor cells (M-MDSC) as a potential biomarker. In the evaluable population, higher baseline M-MDSC levels were associated with worse outcomes on immunotherapy (HR 1.25 per log increase), suggesting these cells may play a role in resistance to dual checkpoint blockade. This finding could help identify which people are most likely to benefit from the combination.
What This Means for People with Mesothelioma
CheckMate-743 remains the landmark trial that changed first-line treatment for pleural mesothelioma. The five-year data confirms that immunotherapy offers something chemotherapy could not: durable, lasting responses for a meaningful number of people.
For people newly diagnosed with unresectable pleural mesothelioma, these numbers frame the conversation with their oncologist. A 14% chance of being alive at five years with immunotherapy, compared to 6% with chemotherapy, is a meaningful difference in a disease with historically poor outcomes.
No new safety signals were identified at five years. The long-term safety profile remained consistent with earlier reports.
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CheckMate-743 is a Phase 3 clinical trial that compared the immunotherapy combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) against standard chemotherapy in 605 people with previously untreated, unresectable malignant pleural mesothelioma. Based on the initial results, the FDA approved this combination in October 2020.
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The original data showed a three-year survival rate of 23% with immunotherapy versus 15% with chemotherapy. At five years, the rates are 14% versus 6%. The survival benefit has held steady, and 17% of people who responded to immunotherapy still had ongoing responses at the five-year mark. No chemotherapy responders maintained their response that long.
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People with non-epithelioid mesothelioma (sarcomatoid or biphasic subtypes) showed the largest benefit, with a 52% reduction in death risk. However, the combination also demonstrated meaningful benefit in epithelioid disease, the most common subtype.
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Yes. Nivolumab plus ipilimumab has been FDA-approved as first-line treatment for unresectable malignant pleural mesothelioma since October 2020. It is administered intravenously at cancer centers. A subcutaneous formulation of nivolumab (Opdivo Qvantig) was also recently approved, reducing infusion time.
References
(2026-02-26). Five-Year Outcomes From CheckMate 743: Nivolumab Plus Ipilimumab vs Chemotherapy in Unresectable Malignant Pleural Mesothelioma.
https://ascopubs.org/doi/10.1200/JCO-25-01328
(2026-02-26). CheckMate 743: 5-Year Survival Data.
https://oncodaily.com/new-paper-alert/checkmate-743-5-year-survival