First-line nivolumab plus ipilimumab versus chemotherapy for unresectable pleural mesothelioma: 5-year outcomes from CheckMate 743

The multinational phase 3 CheckMate 743 trial compared first-line nivolumab plus ipilimumab versus chemotherapy (cisplatin of carboplatin, plus pemetrexed) for unresectable pleural mesothelioma (uPM). Five-year clinical outcomes have now been published. Overall, 303 and 302 patients were randomly assigned to the nivolumab plus ipilimumab and chemotherapy arms, respectively; 300 and 284 patients received the respective study treatments. With a median follow-up of 66.8 months, nivolumab plus ipilimumab demonstrated continued overall survival (OS) benefit versus chemotherapy in all randomized patients (5-year OS rates 14% versus 6%; HR 0.74; 95% CI 0.62-0.88); similar benefit was pbserved 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. 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 0,53-0.78). No new safety signals were observed. The authors conclude that these results demonstrate long-term, durable clinical benefit with nivolumab plus ipilimumab versus chemotherapy among uPM patients.