OBJECTIVES: This systematic review aims to identify studies assessing pharmacological interventions in adult patients with advanced non-small cell lung cancer (aNSCLC) with METex14 skipping alterations who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.

METHODS: Longitudinal studies evaluating MET inhibitors, chemotherapy and/or immunotherapy on previously treated METex14 altered aNSCLC were searched in PubMed, Embase, and CENTRAL databases (May 2024). Studies including >50% of patients on second-line treatment or beyond (2L+) were eligible for inclusion. The outcomes analysed were overall survival (OS), progression free survival (PFS), and objective response rate (ORR).

RESULTS: Ten studies were identified: 4 non-controlled clinical trials (CTs), 2 real-world data (RWD) studies on MET-inhibitors (tepotinib in CTs; capmatinib and crizotinib in both CTs and RWD studies), and 4 RWD studies on immunotherapy. Sample sizes ranged between 25-149 patients in CTs and 22-54 patients in RWD studies. In CTs, median OS (months) was 19.3 with tepotinib and 9.5-20.5 with crizotinib.^1-3 OS was not reported for capmatinib.⁴ Median PFS (months) was 11.0 with tepotinib, 5.4 with capmatinib, and 3.6-7.3 with crizotinib. ORR was 45% with tepotinib, 40.6% with capmatinib, and 12%-32% with crizotinib.^1-4 In RWD studies, median OS (months) was 17.2 with capmatinib, 13.7 with crizotinib, and 13.4-19.3 with immunotherapy.^5-10 Median PFS (months) was 1.9-4.9 with immunotherapy.^7-10 ORR was 50% with capmatinib, 31% with crizotinib, and 17%-35.7% with immunotherapy.^5-10

CONCLUSIONS: In CTs, OS was numerically higher in the VISION-trial (tepotinib) than in the AcSé-trial (crizotinib) and comparable to the finding in PROFILE-1001-trial (crizotinib), but the latter included first-line patients (38%), whereas the first two only included 2L+ patients. PFS and ORR were numerically higher with tepotinib than with other MET-inhibitors. Only phase II CTs are available for decision-making and evidence from RWD studies is scarce, with immunotherapy not bringing additional benefit for the MetEx14 population.