1381P TOGETHER: Pooled real-world datasets of METex14 skipping NSCLC and adjusted comparison of upfront (chemo-)immunotherapy with tepotinib from VISION

The TOGETHER study was designed for flexible pooling of METex14 skipping non-small cell lung cancer (NSCLC) patient (pt) datasets to characterize real-world (rw) outcomes before approval of MET inhibitors. Seven datasets were used to analyze rw progression-free (rwPFS) and overall (rwOS) survival in advanced NSCLC with METex14 skipping according to Kaplan-Meier. Indirect treatment comparisons (ITC) were performed with propensity score reweighting of pts who received first-line (1L) immunotherapy (IO) alone or with chemotherapy (chemo) to match the characteristics of 111 pts with positive tissue biopsies (T+) who received 1L tepotinib in the VISION study (NCT02864992; data cut: Nov 2022). As of Jan 2023, TOGETHER included 309 pts (mean [SD] age 71.1 [9.7] years, 48% male, 52% with smoking history [SM]), with 615 lines of therapy administered between 2004 and 2022. For 1L IO+chemo (n=26; mean age 66.8 [SD 12.4], 65% SM) median rwPFS in TOGETHER was 5.7 months (95% CI: 3.1, 17.5) before and 6.9 mo (95% CI: 5.7, 29.4) after weighting, compared with 15.9 mo (95% CI: 11.3 , ne) for 1L tepotinib (HR 0.52 [0.29, 0.93]; p=0.03). For 1L IO monotherapy (n=48; mean age 73.2 [SD 9.1], 67% SM), median rwPFS in TOGETHER was 3.9 mo (95% CI: 2.7, 7.1) before and 3.4 mo (95% CI: 2.0, 9.7) after weighting compared with 15.9 mo for 1L tepotinib (HR 0.37 [0.24, 0.58]; p<0.01). Although confounded by subsequent treatments, median OS was also longer for tepotinib with 29.7 mo (95% CI: 19.1, ne) compared with 22.1 mo (95% CI: 12.6, ne) for IO+chemo (HR 0.77; p=0.38) and 18.9 mo (HR 0.64; p=0.05) for IO monotherapy. Other rw 1L treatments were chemo (n=128; mean age 69.3 [SD 9.5], 55% SM) with a median rwPFS of 4.8 mo (95% CI: 4.1, 6.2), and crizotinib (n=62; mean age 74.6 [SD 11.0], 56% SM) with a median rwPFS of 7.4 mo (95% CI: 4.4, 10.9). Median rwPFS was shorter for 2L+ chemo (4.3 mo, n=95) or 2L+ IO monotherapy (3.3 mo, n=83), and longer for 2L+ crizotinib (8.1 mo, n=68). This large retrospective analysis shows poor rw outcomes for METex14 skipping NSCLC pts under standard treatments prior to the uptake of novel MET inhibitors. Matched ITC suggests longer PFS and OS with 1L tepotinib compared with 1L IO+chemo or IO monotherapy.