Matching-Adjusted Indirect Comparison (MAIC) of Tepotinib With Capmatinib in Previously Treated Advanced Non-Small Cell Lung Cancer (aNSCLC) With MET Exon 14 (METex14) Skipping

OBJECTIVES: Evidence for targeted therapies in patients with METex14 skipping NSCLC is based on single-arm Phase I/II trial data. However, differences in patient populations between studies make side-by-side comparisons unreliable. The MAIC method provides a more accurate comparison of study data by adjusting for differences in baseline characteristics. Given the approval of the MET TKIs tepotinib and capmatinib in Europe for patients with METex14 skipping aNSCLC who require further treatment following immunotherapy and/or platinum‑based chemotherapy, we compared outcomes using MAICs of data from the VISION study, weighted for comparison with the GEOMETRY mono-1 study, in previously treated patients (2L+) identified by tissue biopsy. Data for comparisons with other available TKIs were unavailable for 2L+.

METHODS: Patient-level data from VISION were weighted using baseline characteristics prognostic for overall survival (OS) (identified by Cox regression) and compared with the GEOMETRY mono-1 population. Overall response rate (ORR), progression‑free survival (PFS), OS, and duration of response (DOR) were compared between the studies. Odds ratios were calculated for ORR comparisons. Reconstructed Kaplan–Meier curves or median outcome point estimates calculated by MAIC were used to compare time‑to‑event endpoints.

RESULTS: The weighting process successfully produced VISION cohorts with baseline characteristics that matched the GEOMETRY mono-1 cohorts, while retaining most of the eligible VISION patients. No consistent difference in ORR in 2L+ was identified. Comparisons suggested an improved PFS (HR 0.54; 95% CI: 0.36, 0.83) and OS (HR 0.66; 95% CI: 0.42, 1.06) with tepotinib, but estimates of median DOR were comparable between the studies (11.1 and 9.7 months for tepotinib and capmatinib, respectively). Data in second-line only will be presented.

CONCLUSIONS: This MAIC identifies potential differences in the efficacy profiles of tepotinib and capmatinib. There is tendency towards probability of superiority for PFS in favor of tepotinib, however, results must be interpreted cautiously due to possible unobserved confounders.