Fig. 2: Analyses of tumor-intrinsic genomic determinants of sotorasib response and resistance.
From: Molecular determinants of sotorasib clinical efficacy in KRASG12C-mutated non-small-cell lung cancer
a, Oncoprint of alterations (pathogenic or potentially pathogenic based on OncoKB, SnpEff and FATHMM designation) in patients with available tissue NGS data at baseline (CB100 + CB200 sotorasib and docetaxel arms). The rows indicate genes with reported alterations (short variants, copy number variants (gain or loss), insertions, deletions or fusions) sorted based on prevalence. Of note, 10 patients from CB200 (3.2% of patients across both CodeBreaK studies) were negative for KRASG12C by retrospective tissue NGS. However, 8 of 10 patients were still reported to be KRASG12C positive by the plasma ctDNA assay. Tissue heterogeneity and sample quality likely account for this discordance. All patients, including those with lack of KRASG12C detection by retrospectively performed tissue NGS, had prospective central laboratory confirmation of KRASG12C in tissues using the pre-defined diagnostic companion assay (KRAS RGQ PCR Kit (Qiagen)). Hence, these patients were included in the analyses. b, Forest plot showing hazard of progression (HR (95% CI)) with sotorasib compared to docetaxel treatment in CB200 patients grouped based on specified genomic alterations. FDR-adjusted, two-sided P values for the interaction between arm and gene alteration in Cox proportional hazards models are noted. c,d, Kaplan–Meier curves of PFS according to ATM mutation status in patients treated with sotorasib or docetaxel (CB200). e, Kaplan–Meier curve of PFS according to ATM mutation status in patients treated with sotorasib from the combined dataset. f,g, Kaplan–Meier curves of PFS (f) or OS (g) according to KEAP1 mutation status in patients treated with sotorasib in the combined dataset. CNV, copy number variation; MUT, mutant; NE, not estimable.
