OBJECTIVES: Tepotinib, a highly selective MET inhibitor, has been approved in multiple countries for treatment of NSCLC with METex14 skipping based on the single-arm Phase II VISION trial (NCT02864992). We conducted an indirect treatment comparison to evaluate the comparative effectiveness of tepotinib versus standard of care therapies used in EGFR-/ALK-negative NSCLC.

METHODS: The dataset included patients treated with tepotinib in VISION Cohort A (data cut-off: Feb 01, 2021) and retrospective, patient-level data from patients with EGFR-/ALK-negative METex14 skipping NSCLC, treated with chemotherapy or immunotherapy in real-world clinical practice. To minimize differences in baseline characteristics, observational data were reweighted to match the VISION cohort using propensity scoring with standardized mortality ratio weighting. The propensity score covariates were informed by expert clinical input and included prior treatment status, mean age, metastatic disease status, sex, adenocarcinoma histology, and smoking history.

RESULTS: After weighting, the tepotinib (n=151), chemotherapy (n=66), and immunotherapy (n=51) groups were generally well-balanced with respect to prior treatment (54.3%, 56.7%, and 53.2%, respectively), mean age (73 years in all groups), presence of metastatic disease (98.0%, 98.3%, 100.0%), male sex (52.3%, 53.7%, 56.0%), adenocarcinoma histology (86.8%, 87.9%, 87.1%), and smoking history (51.7%, 51.6%, 49.9%). Median progression-free survival (PFS) was markedly higher with tepotinib (8.6 months by investigator assessment) compared with chemotherapy (3.2 months) or immunotherapy (3.9 months). Higher median overall survival was also observed with tepotinib (19.1 months) versus comparators (chemotherapy, 15.5 months; immunotherapy, 18.9 months). Subgroup analyses of treatment-experienced and treatment-naϊve patients showed similar trends.

CONCLUSIONS: This analysis demonstrates the benefit of tepotinib in a balanced cohort of patients with METex14 skipping NSCLC. Compared with immunotherapy or chemotherapy, PFS was higher with tepotinib in a population with both a poor prognosis and response to standard treatments for EGFR-/ALK-negative NSCLC.