Long-term real-world outcomes of nivolumab+ipilimumab treatment of unresectable pleural mesothelioma: update of...

CheckMate-743 trial results led to nivolumab+ipilimumab becoming the standard first-line therapy for unresectable pleural mesothelioma (uPM), but real-world (rw) long-term follow-up evidence remains limited.

This updated nationwide retrospective analysis of rw-efficacy and -safety of that combination therapy for uPM in a French early-access program (Meso-Immune) included progression-free survival (rw-PFS), overall survival (rw-OS), objective response rate (ORR) and immune-related adverse events (irAEs). Post-progression efficacies of second- and third-line therapies were also assessed.

Among 204 uPM patients (median age 75 years) included, histology was epithelioid for 152 (75%) and non-epithelioid for 52 (25%), 55% had breast-cancer-1-associated protein-1 (BAP1) loss. At median 30-month follow-up, median rw-(m)PFS (95% CI) lasted 6.3 (5.3-7.9) months, with 13.8% PFS rate. For the 117 (75%) and 67 (89%) patients given, respectively, second/third-line therapies: median rw-mPFS2/3 lasted 6.9 (6.1-8.2)/3.1 (2.6-5.3) months and ORR2 reached 28.2% (20.0-37.6%). mOS lasted 20.2 (17.6-23.0) months, 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: grade ≥ 3 irAEs occurred in 24.2% of all treated patients; grade 5 irAEs occurred in 6.4%. Toxicities necessitated treatment discontinuation for 39.3% and hospitalization for 34.3%.

This rw-analysis showed that combination nivolumab+ipilimumab for uPM provided long-term durable clinical benefit, comparable to CheckMate-743, despite an older population, with subsequent therapies retaining efficacy, especially for epithelioid subtype. These findings support first-line nivolumab+ipilimumab standard-of-care and underscore the need to improve beyond second-line strategies.