Nivolumab+ipilimumab shows 5-year OS benefit (14% vs 6%) vs chemo in unresectable pleural mesothelioma

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