Indirect comparison of the effectiveness of tepotinib and immunotherapy in NSCLC with METex14 skipping alterations: Final propensity-scored analysis of eight pooled real-world datasets (TOGETHER) vs the VISION trial.

e20751 Background: Tepotinib demonstrated clinical efficacy in NSCLC patients with MET ex14 skipping alterations in the single-arm VISION trial. Comparative effectiveness estimates against the contemporary therapeutic option of immunotherapy (IO) with or without chemotherapy (CT), were generated using external data. Methods: Eight international real-world datasets, which included patients who started treatment between 2010 and 2022 were pooled to form a real-world cohort. Inclusion and exclusion criteria based on VISION were applied to ensure generalizability and propensity scoring used to address differences in observed characteristics, stratifying by previous treatment status. Variables used were mean age, advanced vs. metastatic disease, sex, adenocarcinoma histology, and smoking history. Reweighted data were used to facilitate comparisons of real-world progression-free (PFS) and overall survival (OS) outcomes between therapy regimens in the first line (1L), second or later line (2L+), or line agnostic setting (LAs). Results: TOGETHER yielded information on 45 and 24 patients receiving IO or IO+CT in 1L, 83 and 6 patients in 2L+, respectively. In LAs 146 patients received IO±CT. TOGETHER patients were reweighted to match baseline characteristics of patients in VISION. As shown in the table (survival time in months), in 1L median (m) PFS was longest and the 24-month survival proportion was highest for tepotinib, compared to IO and IO+CT. In 2L+, due to the single digit sample size for those receiving IO+CT, only IO and IO±CT could be compared, with tepotinib showing longer mPFS and higher 24-month PFS. Due to the effects of prior or subsequent treatment lines which cannot be accounted for, 1L and 2L+ OS estimates are confounded; this notwithstanding, analyses of LAs showed the following: mOS for tepotinib was 19.2 months, compared to 19.0 for IO and 16.7 for IO±CT. Conclusions: Although MET ex14 skipping alterations are rare in NSCLC, pooling real-world datasets provided sufficient patient numbers to allow for comparative effectiveness estimates. In propensity score weighted analyses, tepotinib demonstrated longer PFS versus IO, as monotherapy or in combination with CT. The short PFS across comparators underlines the poor prognosis for patients with existing therapies, while also confirming tepotinib as an effective treatment option in this rare, biomarker-driven NSCLC subtype. Tepotinib IO IO+CT IO±CT 1L n 164 45 24 67 mPFS [95% CI] 8.7 [8.2, 12.6] 5.2 [2.7, 12.4] 8.0 [3.0, 17.5] 4.3 [2.7, 9.7] 24-month PFS 30% 13% Not reached 8% 2L+ n 149 83 6 88 mPFS [95% CI] 8.3 [7.0, 11.0] 4.8 [3.2, 7.7] - 4.8 [3.2, 7.7] 24-month PFS 19% 12% - 11% Line agnostic n 313 121 29 146 mOS [95% CI] 19.2 [16.3, 22.3] 19.0 [14.9, 22.4] 13.6 [12.3, 23.1] 16.7 [13.7, 21.7] 24-month OS 41% 33% 7% 32%