Open AccessCurrent views on tumor mutational burden in patients with non-small cell lung cancer treated by immune checkpoint inhibitors
Author(s) -
Léa Berland,
Simon Heeke,
Olivier Humbert,
Adam Macocco,
Elodie LongMira,
Sandra Lassalle,
Virginie LespinetFabre,
Salomé Lalvée,
Olivier Bordone,
Charlotte Cohen,
Sylvie Leroy,
Véronique Hofman,
Paul Hofman,
Marius Ilié
Publication year - 2019
Publication title -
journal of thoracic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.682
H-Index - 60
eISSN - 2077-6624
pISSN - 2072-1439
DOI - 10.21037/jtd.2018.11.102
Subject(s) - medicine , immunotherapy , lung cancer , context (archaeology) , biomarker , pd l1 , oncology , atezolizumab , nonsynonymous substitution , cancer , cancer research , nivolumab , gene , biology , paleontology , genome , biochemistry
In the last few years, the treatment of patients with non-small cell lung cancer (NSCLC) has impressively benefitted from immunotherapy, in particular from the inhibition of immune checkpoints such as programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1). However, despite the significant survival benefit for some patients with advanced NSCLC, the objective response rates (ORRs) remain relatively low no more than 20-30% with a large proportion of patients demonstrating primary resistance. Although the selection of NSCLC patients for the first-line treatment is currently guided by the expression of PD-L1 in tumor cells as detected by immunohistochemistry, this is not the case for the second-line setting. Moreover, the sensitivity and specificity of PD-L1 expression is modest which has prompted the search for additional predictive biomarkers. In this context, the assessment of the tumor mutational burden (TMB), defined as the total number of nonsynonymous mutations in the coding regions of genes, has recently emerged as an additional powerful biomarker to select patients for immunotherapy. The purpose of our review is to highlight the recent advances as well as the challenges and perspectives in the field of TMB and immunotherapy for patients with NSCLC.