Exome Analysis Reveals Genomic Markers Associated with Better Efficacy of Nivolumab in Lung Cancer Patients

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Corentin RichardFrançois Ghiringhelli

Abstract

Immune checkpoint inhibitors revolutionized the treatment of non-small cell lung cancer (NSCLC). However, only one-quarter of patients benefit from these new therapies. PD-L1 assessment and tumor mutational burden (TMB) are available tools to optimize use of checkpoint inhibitors but novel tools are needed. Exome sequencing could generate many variables but their role in identifying predictors of response is unknown. We performed somatic and constitutional exome analyses for 77 patients with NSCLC treated with nivolumab. We studied: one-tumor-related characteristics: aneuploidy, CNA clonality, mutational signatures, TMB, mutations in WNT, AKT, MAPK, and DNA repair pathways, and two-immunologic characteristics: number of intratumoral TCR clones, HLA types, and number of neoantigens; and six clinical parameters. A high TMB per Mb, a high number of neoantigens, mutational signatures 1A and 1B, mutations in DNA repair pathways, and a low number of TCR clones are associated with greater PFS. Using a LASSO method, we established an exome-based model with nine exome parameters that could discriminate patients with good or poor PFS (P < 0.0001) and overall survival (P = 0.002). This model shows better ability to predict outcomes compar...Continue Reading

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Citations

May 23, 2019·Molecular Cytogenetics·Andréa E TijhuisSarah E McClelland
Aug 18, 2020·Current Oncology Reports·Camille TravertPascale Tomasini
Oct 6, 2020·Scandinavian Journal of Immunology·Andreas HallqvistSukanya Raghavan
Oct 29, 2020·International Journal of Immunogenetics·Milena Ivanova, Velizar Shivarov
Nov 3, 2020·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Arthur KrauseLukas Bubendorf
Feb 9, 2021·World Journal of Clinical Cases·Min ChenHai-Tao Wu
Feb 26, 2021·Seminars in Cancer Biology·Yin WuCharles Swanton
Apr 13, 2020·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Jean-David FumetFrancois Ghiringhelli
Jun 12, 2020·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Lynette M ShollJohn W Longshore

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