Efficacy and safety of tepotinib in MET‑altered non‑small cell lung cancer: a meta-analysis.

MET exon 14 skipping mutations (METex14) or amplification drives a subset of non-small cell lung cancer (NSCLC). Tepotinib, a selective MET tyrosine kinase inhibitor (TKI), has shown promise in early trials; however, comparative efficacy and safety data across MET-altered subpopulations remain limited. This systematic review of six studies (546 patients) assessed the clinical outcomes of Tepotinib in METex14 or MET-amplified NSCLC. The primary endpoint was objective response rate (ORR); secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. The pooled objective response rate (ORR) was 52% (95% CI: 48–56%) and a disease control rate (DCR) of 76% (95% CI: 72–80%). Median PFS was 10.16 months, and median OS was 14.67 months. Subgroup analyses revealed no significant differences in ORR between METex14 (52%) and MET amplification (53%, p = 0.905) or between monotherapy (51%) and combination therapy (56%, p = 0.242). Common treatment-related adverse events (TRAEs) were grade 1–2 peripheral edema (50%) and diarrhea (36%); grade ≥ 3 TRAEs were infrequent (8% for edema). In conclusion, Tepotinib demonstrated comparable efficacy in METex14 and MET-amplified NSCLC with a manageable safety profile. The PFS benefit of combination therapy warrants further randomized trials. These findings support Tepotinib as a valuable therapeutic option for MET-altered NSCLC.