53P MET exon 14 skipping mutations in non-small cell lung cancer: Real-world data from the Italian biomarker ATLAS database

MET exon 14 skipping mutation (METex14) is a rare alteration in non-small cell lung cancer (NSCLC). Here we report disease and patients characteristics, efficacy and tolerability of MET inhibitors among advanced METex14 NSCLC patients from the Italian real-world registry ATLAS. Clinical, pathological and molecular data, treatment efficacy/tolerability outcomes were retrospectively collected from patients' medical charts and electronic healthcare records from the ATLAS registry. From July 2020 to July 2023 a total of 146 METex14 advanced NSCLC patients were included across 27 Italian centers. Median age was 74 years old (range 46-92). Most patients were male (52%), with ECOG- PS <2 (72%) and adenocarcinoma subtype (83%). 24% had brain metastases. Overall, 56 (38%) patients were treated with capmatinib and 34 (23%) with tepotinib. Among patients treated with MET inhibitors, 29% and 52% of them received targeted treatment in 1st and 2nd line, respectively. Response rate (RR) was 37% (33% in previously treated and 46% in treatment-naïve patients) with a disease control rate of 62%. With a median follow up of 10.8 months, progression free survival (PFS) was 6.6 months (95% CI: 4.3-8.3). In patients receiving MET inhibitor in 1st, 2nd and further lines, PFS was 7.2 (95% CI: 4.3-10.4), 6.6 months (95% CI: 5.1-11.2) and 3.9 months (95% CI: 2.7-8.7), respectively. Overall survival was 10.7 months (95% CI: 7.2-19.3). In patients with measurable brain metastases (17 cases), the intracranial RR was 41%. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 12% of patients with grade 3 peripheral edema in 7% of cases. A fatal adverse reaction occurred in one patient due to pneumonitis. TRAEs-related dose reduction and discontinuation were reported in 6% and 8% of cases. Capmatinib and tepotinib represent an effective treatment option in NSCLC patients with MET exon 14 skipping mutation. Real-world efficacy outcomes are worse than those reported in prospective clinical trials. MET inhibitor activity is more pronounced in the treatment-naïve population, suggesting that this is the right setting in the METex14 therapeutic strategy management.