Nintedanib as switch maintenance treatment in malignant pleural mesothelioma (NEMO): A double-blind randomized phase II trial (EORTC-08112-LCG)

INTRODUCTION: Pleural mesothelioma (PM) is a lethal malignancy in which angiogenesis and progressive fibrosis drives disease. We evaluated angiogenesis inhibition using nintedanib monotherapy as switch maintenance in patients with PM that completed 4-6 cycles of prior platinum-pemetrexed chemotherapy. The trial was performed in parallel to the LUME-Meso trial in an era prior to routine immune checkpoint inhibitor use, when platinum-pemetrexed was standard of care. METHODS: This is a triple-blind, placebo-controlled, multicentric, randomized, phase II study. Patients with inoperable PM (all histologies) that completed 4-6 cycles of platinum-pemetrexed chemotherapy were randomized to nintedanib or placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. RESULTS: The trial was prematurely closed due to poor accrual after LUME-meso reported. 37 patients were randomized (18 to nintedanib, 19 to placebo). All analyses performed were descriptive. The median PFS was 3.4 months (95% CI: 2.83-5.82) and 4.6 months (95% CI: 3.65-13.17) for nintedanib and placebo arms, respectively (HR = 2.25, 95% CI: 1.07-4.73) with corresponding median OS of 13.1 months (95% CI: 10.22-26.02) and 38.9 months (95% CI: 18.66-NE) for nintedanib and placebo arms, respectively (HR = 2.38, 95% CI: 1.05-5.43). Two patients (11.1%) in the nintedanib arm experienced ≥ grade 3 treatment-related adverse events. Post progression treatment was balanced between arms but more patients in the placebo arm received immunotherapy (87% vs 54%). CONCLUSIONS: Descriptive analyses suggest switch maintenance nintedanib does not improve PFS nor OS compared to placebo. Efficacy of the placebo arm may be related to imbalanced immunotherapy usage.