OBJECTIVES: With the approval of immunotherapies (IOs) and IO combinations with chemotherapy (IO+chemo), several IO-based treatment options are available for non‑oncogenic NSCLC. However, in specific mutations such as METex14 skipping, observational studies suggest IOs do not perform as well, and no evidence exists for IO+chemo in this population. By pooling seven real-world datasets of patients with METex14 skipping NSCLC (the TOGETHER study), we are able to compare IO-based treatments to tepotinib, a selective MET inhibitor.

METHODS: TOGETHER includes 289 previously untreated patients, 47 of whom received IO, and 26 IO+chemo, facilitating comparisons with the 164 previously untreated patients from the tepotinib VISION study (NCT02864992). Time-to-event outcomes are compared with the November 2022 data cut-off of VISION, using propensity scoring to account for differences in patient characteristics based on clinical input; reweighting IO treatment data to match VISION.

RESULTS: After weighting, patient and disease characteristics were balanced across groups, with no statistical differences observed. Patients who received tepotinib had longer progression-free survival (PFS, median 8.7 months) than patients receiving IO (median 3.6, Cox Hazard Ratio (HR) 0.56 [95% confidence interval (CI): 0.37, 0.85]) and IO+chemo (median 6.7, HR 0.43 [95% CI: 0.43, 1.12]). Overall survival comparisons marginally favored tepotinib (median 21.3 months) over IO (median 19.0, HR 0.85 [95% CI: 0.57, 1.28]), and IO+chemo (median 19.3, HR 0.97 [95% CI: 0.57, 1.66]).

CONCLUSIONS: Although the introduction of IO has led to a step change in non-oncogenic NSCLC, in patients with METex14 skipping NSCLC, consistent with published observational data, we find time-to-event outcomes to be shorter. Despite limited patient numbers, the evidence presented suggests similarly patterns for IO+chemo. Estimated PFS is longer with tepotinib, while evidence on overall survival remains uncertain and confounded by subsequent treatment use, but does suggest a differential outcome for any treatment in isolation.