Fig. 2.

Flow diagram of the study. (A) Part 1a, Mirror comparisons of the impact of TMB-High vs TMB-Low on the ICI-containing therapy compared to chemotherapy. (B) Part 1b, Mirror comparisons of progression-free survival of anti-PD-L1 vs anti-PD-1 inhibitors. (C) Part 2, Network diagram of comparisons on progression-free survival of all first-line treatments. The circle size is proportional to the number of patients with TMB-Low receiving the regimen (in red brackets), and the number of patients with TMB-High receiving the regimen is given in yellow brackets. The number of patients receiving ICI and chemotherapy in Impower110 TMB-Low group is unavailable. (D) Part 3, Multi-cohort validation of the effect of TMB on ICI-contained therapy. Abbreviations: 1L, first-line treatment; ≥2L, second or more line treatment; bTBM, blood-based tumor mutation burden; CGP, cancer gene panel; Chemo, chemotherapy; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; Doce, docetaxel; HR, hazard ratio; ICIs, immune checkpoint inhibitors; P-Chemo, platinum-based doublet chemotherapy; PD-1, programmed cell death 1; PD-L1, programmed cell death-ligand 1; PFS, progression-free survival; tTMB, tissue-based tumor mutation burden; WES, whole exosome sequencing.