Clinical Activity of MET-TKIs in METex14 Skipping NSCLC With Poor Performance Status

Background/Aim: The mesenchymal-epithelial transition (MET) receptor plays a key role in cell growth and survival. The MET exon 14 (METex14) skipping mutation occurs in 3% to 4% of patients with non-small cell lung cancer (NSCLC) and leads to prolonged MET signaling and oncogenesis. MET tyrosine kinase inhibitors (TKIs), such as tepotinib and capmatinib, are effective for METex14-altered NSCLC; however, their impact on patients with a poor performance status (PS) is unclear. We retrospectively analyzed clinical outcomes of MET-TKI treatment for NSCLC with the METex14 skipping mutation. Patients and Methods: We reviewed 59 cases of NSCLC with the METex14 skipping mutation diagnosed at the National Cancer Center Hospital between June 2020 and April 2024. Clinical data included demographics, PS, histology, PD-L1 expression, treatment response, progression-free survival (PFS), and overall survival (OS). Results: Forty-nine patients (median age, 72 years; range=50-87 years; 53.1% male) received MET-TKIs (tepotinib or capmatinib). Thirty-seven patients and 12 patients had PS scores of 0 or 1 and ≥2, respectively. The median PFS and median OS of patients who received MET-TKI treatment were 5.6 months and 18.7 months, respectively. Thirty-seven patients who received first-line MET-TKI treatment had median PFS, median OS, and a median overall response rate (ORR) of 5.6 months, 21.3 months, and 48.6%, respectively. For patients with a PS score ≥2 (n=9), the median PFS, median OS, and median ORR were 0.95 months, 1.3 months, and 11.1%, respectively. A PS score ≥2 was strongly associated with shorter OS. Two of nine (22.2%) patients with a poor PS experienced improvement. Conclusion: MET-TKIs are effective for NSCLC with the METex14 skipping mutation; however, their efficacy for patients with a poor PS is limited.