Abstract
Immune checkpoint inhibitors radically changed the treatment of patients with non-small cell lung cancer (NSCLC). However, only one-quarter of patients benefit from these new therapies when used as monotherapy. The assessment of Program Death Ligand-1 (PD-L1) tumor expression by immunohistochemistry is used to select potential responder patients, but this not an optimal marker since it does not predict the absence of anti PD-1 efficacy. Despite this shortcoming, PD-L1 remains the gold standard biomarker in many studies and the only biomarker available for clinicians. In addition to histological markers, transcriptomic and exome analyses have revealed potential biomarkers requiring further confirmation. Recently, tumor mutational burden has emerged as a good surrogate marker of outcome. In this review we will detail current knowledge on DNA and RNA related biomarkers.
Highlights
Lung cancer is a major public health issue and the leading cause of cancer-related death worldwide.In 2012, 1.8 million new cases were diagnosed worldwide, representing about 13% of all detected cancers [1]
Pembrolizumab and Atezolizumab are antibodies directed against Program Death 1 (PD-1) or Program Death Ligand-1 (PD-L1) that disrupt the engagement of PD-1 with its ligands (PD-L1 and 2) and prevent inhibitory signals in T cells
The OAK study that tested Atezolizumab in patients with advanced or metastatic non-small cell lung cancer (NSCLC) previously treated by chemotherapy used a composite score evaluating the expression of PD-L1 by tumor cells and tumor microenvironment immune cells, whereas the clinical trials evaluating the efficacy of Nivolumab or Pembrolizumab in the same indication evaluated the expression of PD-L1 only in tumor cells
Summary
Lung cancer is a major public health issue and the leading cause of cancer-related death worldwide. The OAK study that tested Atezolizumab in patients with advanced or metastatic NSCLC previously treated by chemotherapy used a composite score evaluating the expression of PD-L1 by tumor cells and tumor microenvironment immune cells, whereas the clinical trials evaluating the efficacy of Nivolumab or Pembrolizumab in the same indication evaluated the expression of PD-L1 only in tumor cells. Ilie et al compared PD-L1 expression between preoperative biopsies and the corresponding lung resection in 160 patients presenting an NSCLC They found major discordances in PD-L1 expression between the biopsies and the tumor samples [27]. Thereby, PD-L1 expression is an interesting biomarker to try to select patients who might be prone to respond to anti PD-1/PD-L1 therapies This biomarker is imperfect, especially nowadays that treatment combinations (chemotherapy + anti-PD-L1/PD-1 antibody), are an option as a first line of treatment for advanced or metastatic NSCLC patients. It is essential to find a more specific and sensitive biomarker to select patients who are more likely to respond to chemotherapy alone, anti-PD-L1/PD-1 antibody alone or combotherapy
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