Characterization of biomarkers to immune checkpoint blockade therapy across solid tumors.

Abstract

26 Background: Immune checkpoint blockade (ICB) therapy has been effective patients with solid tumors. Currently, tumor expression of programmed death-ligand 1 (PD-L1) is clinically used as a biomarker of predicted response to ICBs in non-small cell lung cancer (NSCLC). However, across solid tumors, only a subset of patients benefit from ICBs, so there is need to identify other biomarkers to predict response to ICB. We investigated the use of large panel next generation sequencing (NGS) to characterize biomarkers to ICBs across solid tumors. Methods: NGS and PD-L1 immunohistochemistry (IHC) was performed on a series of solid tumors. NGS analysis included detection of single nucleotide polymorphisms (SNPs), insertions and deletions (indels), copy number variation (CNV), and gene-fusions in 435 cancer-related genes, microsatellite instability (MSI), tumor mutational burden (TMB) based on non-synonymous SNPs, and HPV16/18 and EBV viral status. Genomic alterations in previously reported biomarkers of response to ICBs were assessed. Results: 143 solid tumors were analyzed with NGS and PD-L1 IHC. The samples included 80 NSCLC, 15 colorectal carcinoma, 8 cutaneous melanoma, 6 breast carcinoma, and 34 other solid tumors. The mean TMB varied by tumor type, with the highest in melanoma. The frequency of PD-L1 expression was higher in NSCLC and melanoma compared to colorectal carcinoma. The relationship between PD-L1 expression and the other biomarkers varied by tumor type (Table 1). Positive association (+); Negative association (-): No association (None). Conclusions: We characterized biomarkers to ICBs across a range of solid tumors. We found tumor-specific differences in the mean TMB and frequency of PD-L1 expression. We also found tumor-specific differences in the associations between PD-L1 and other potential biomarkers, including KRAS, NRAs, HRAs, BRAF, and EGFR mutation status. We found no correlation between PD-L1 expression and MSI and viral status. NGS is an efficient platform for analysis of biomarkers in solid tumors.[Table: see text]