Real-world outcomes of nivolumab plus ipilimumab for unresectable pleural mesothelioma: update of Meso-Immune GFPC 04-2021

Based on results of the CheckMate-743 trial, nivolumab plus ipilimumab (nivo+ipi) is the standard first-line therapy for unresectable pleural mesothelioma (uPM), but real-world (rw) long-term follow-up evidence is limited. Long-term follow-up of the French nationwide retrospective Meso-Immune GFPC 04-2021 study evaluated progression-free survival (rwPFS), overall survival (rwOS), objective response rate (ORR), and immune-related adverse events (irAEs). Among 204 uPM patients (median age 75 years), histology was epithelioid for 75% and non-epithelioid for 25%); 55% had breast-cncer-1-associated protein-1 (BAP1) loss. At median 30-month follow-up, median rwPFS on nivo+ipi lasted 6.3 months (95% CI 5.3-7.9). For 117 patients receiving nivo+ipi as second-line therapy median rwPFS2 lasted 6.9 months (95% CI 6.1-8.2) and ORR2 was 28.2% (20.0-37.6) and for 67 patients receiving nivo+ipi as third-line therapy rwPFS3 lasted 3.1 months (2.6-5.3). Median rwOS lasted 20.2 months (95% CI 17.6-23.0) with 23.5% of patients alive at 30 months; it was longer for epithelioid versus non-epithelioid uPM patients (22.3 versus 14.3 months). BAP1 loss did not impact PFS or OS. irAEs occurred in 68.6% of patients, with grade ≥ 3 events in 24.2% and grade 5 events in 6.4%. Toxicities required treatment discontinuation in 39.3% and hospitalization in 34.3%. The authors conclude that this rw-analysis showed that the combination of nivo+ipi for uPM provided long-term clinical benefit, comparable to what was reported for CheckMate-743, despite an older population, with subsequent therapies retaining efficacy, especially for epithelioid subtype.