WCLC 2025 - Posters & ePosters-EP.12.30 Real-World Outcomes of Full and Reduced Dose Capmatinib and Tepotinib Treatment for MET Exon 14 Skipping Mutation NSCLC

EP.12.30 Real-World Outcomes of Full and Reduced Dose Capmatinib and Tepotinib Treatment for MET Exon 14 Skipping Mutation NSCLC

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This study from Northwestern University Feinberg School of Medicine evaluated real-world outcomes of full and reduced dose treatment with capmatinib and tepotinib, FDA-approved MET tyrosine kinase inhibitors (TKIs), in patients with advanced or metastatic non-small cell lung cancer (NSCLC) harboring MET Exon 14 skipping mutations (METex14) or MET amplifications. METex14 mutations occur in about 3% of NSCLC cases.<br /><br />The research included 43 patients (median age 71, 58% female), mostly stage IV (98%), with 84% having METex14 mutations and 16% MET amplifications. Approximately one-third had central nervous system involvement, and half had a history of tobacco use. Prior treatments varied, with 53% treatment-naïve and 42% having received chemotherapy.<br /><br />Among the 28 patients treated with capmatinib, 82% achieved stable disease (SD) or partial response (PR) as their best response. Dose reductions for adverse events (AEs) occurred in 52% of responders, typically around 63 days after treatment initiation. Four patients began at reduced doses due to age and performance status (PS). Median progression-free survival (PFS) was 11 months for full dose and 13 months for reduced dose capmatinib (p=0.19).<br /><br />For the 15 treated with tepotinib, 80% had SD or PR. Dose reductions were needed in 41% of responders, occurring around 28 days after start. Two patients started on reduced doses for similar reasons. Median PFS was 9 months at full dose versus 11 months at reduced dose (p=0.74).<br /><br />Common AEs leading to dose reduction included edema and liver function abnormalities for capmatinib, and nausea and edema for tepotinib.<br /><br />The data suggest that reduced dosing of MET TKIs, often required in older patients with comorbidities or due to AEs, offers comparable clinical benefit to full dosing in METex14 NSCLC, supporting dose flexibility in real-world clinical practice.

Asset Subtitle

Joseph Fuchs

Meta Tag

Speaker Joseph Fuchs

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

METex14 mutations

NSCLC

capmatinib

tepotinib

MET tyrosine kinase inhibitors

dose reduction

progression-free survival

adverse events

real-world outcomes

non-small cell lung cancer