Immune checkpoint inhibitor (ICPI) efficacy and resistance detected by comprehensive genomic profiling (CGP) in non-small cell lung cancer (NSCLC)

摘要: Background: The prediction of outcome to ICPI in advanced NSCLC is of great clinical interest. We considered CGP, PD-L1 IHC, and real world data to investigate potential biomarkers for ICPI response.Methods: CGP and IHC was performed on 1,619 FFPE NSCLC samples in the FoundationCORE database (FMI). The SP142 antibody was used to capture PD-L1 tumor expression (PD-L1 TE) for these 1,619 samples. NSCLC patients (n= 2139) in the Flatiron Health Analytic Database with FoundationOne testing CGP results and real world IHC results for PD-L1 TE were analyzed separately (FMI-FIH). CGP used≥ 50 ng of DNA and a hybrid-capture, adaptor ligation-based assay (median coverage depth> 600X). TMB (mut/Mb) was determined on 1.1 Mb of sequenced DNA.Results: PD-L1 IHC TE correlated weakly with TMB (FMI samples)(Spearman’s ρ 0.085, p= 6.16 e-4); mean TMB was 10.9 mut/Mb, median 8.1 …