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

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.

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).

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.

MET-TKIs are effective for NSCLC with the METex14 skipping mutation; however, their efficacy for patients with a poor PS is limited.