Over the past few years, the development of immune checkpoint inhibitors has altered the treatment paradigm in non–small cell lung cancer (NSCLC). Enrichment strategies have identified programmed death-ligand 1 (PD-L1) staining by immunohistochemistry to be a predictive biomarker in treatment-naive patients with refractory NSCLC. In particular, Keynote-0241 met its primary end points for overall survival (OS) and progression-free survival (PFS) in PD-L1 immunohistochemistry 50% or greater for pembrolizumab compared with platinum-based chemotherapy, validating PD-L1 immunohistochemistry as a biomarker for OS. Tumor mutation burden (TMB) has also emerged as a possible biomarker. The prevalence of somatic mutations among cancers ranges from 0.01 mutations/megabase (Mb) to more than 400 mutations/Mb. Some of these mutations lead to the translation of novel peptide epitopes or neoantigens that should enhance the immunogenicity of the tumor by eliciting T-cell repertoires. Initial studies of TMB were conducted by using whole-exome sequencing on tumor DNA and case-matched germline DNA.
Addeo A, Banna GL, Weiss GJ. Tumor Mutation Burden—From Hopes to Doubts. JAMA Oncol. Published online May 30, 2019. doi:10.1001/jamaoncol.2019.0626
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