OBJECTIVES: The selective MET TKIs tepotinib and capmatinib are approved in the EU to treat advanced METex14 skipping NSCLC after prior chemo- and/or immunotherapy; the non-selective MET TKI crizotinib is sometimes used off-label. Comparative safety is an important factor for payers and decision-makers, but head-to-head data are unavailable.

METHODS: We used MAIC, a pairwise indirect comparison method, to compare safety outcomes with tepotinib versus capmatinib and crizotinib in patients with METex14 skipping NSCLC. MAICs used patient-level data from the VISION trial of tepotinib (NCT02864992: overall N=313, treatment-naïve [1L], n=164; previously treated [2L+], n=149; data cut-off: November 20, 2022), and aggregate data from trials of capmatinib (GEOMETRY mono-1: Cohorts 5b [1L; N=28] and 4 [2L+; N=69]; January 6, 2020) and crizotinib (PROFILE 1001: 1L and 2L+ [N=69]; January 31, 2018). VISION data were reweighted to match baseline characteristics of comparator trials. Safety was compared, overall or by treatment line.

RESULTS: The VISION population was successfully reweighted to match comparator trial populations. In MAICs versus capmatinib, effective sample sizes (ESSs) for tepotinib were 112.3 (1L) and 145.3 (2L+). After reweighting, rates of treatment-related adverse events (TRAEs) leading to treatment discontinuation with tepotinib versus capmatinib were 15% vs 21% in 1L, and 14% vs 20% in 2L+. Any-grade/Grade ≥3 TRAE rates were unavailable for capmatinib. In an MAIC across treatment lines (tepotinib ESS=241.5), rates with tepotinib versus crizotinib were 91% vs 94% for any-grade TRAEs, 32% vs 29% for Grade ≥3 TRAEs, 33% vs 38% for TRAEs leading to dose reduction, and 14% vs 7% for TRAEs leading to treatment discontinuation.

CONCLUSIONS: In MAICs based on available data, safety outcomes with tepotinib were improved versus capmatinib, and comparable versus crizotinib in patients with METex14 skipping NSCLC, further supporting tepotinib as a well-tolerated treatment. These data can assist decision-makers in assessing targeted treatment options for this tumor type.