Programmed Death Ligand 1 (PD-L1) as a Predictive Biomarker for Pembrolizumab Therapy in Patients with Advanced Non-Small-Cell Lung Cancer (NSCLC)

Adv Ther. 2019 Oct;36(10):2600-2617. doi: 10.1007/s12325-019-01057-7. Epub 2019 Aug 20.

Abstract

Recently, immunotherapy has been shown to be an effective and helpful therapeutic option for the treatment of advanced non-small-cell lung cancer (NSCLC). The activity of antitumor T cells may be restored through the checkpoint blockade using anti-programmed death 1 or anti-programmed death ligand 1 (PD-L1) antibodies, showing, in several cancer patients, an increased progression-free survival and overall survival compared with classical chemotherapy. As recently shown by several studies, the PD-L1 expression levels in tumors may offer a selection criterion for patients to predict their immunotherapy response. In particular, NSCLC patients with high tumor PD-L1 levels (proportional score ≥ 50% for first-line therapy and ≥ 1% for second-line treatment, respectively) showed better response rates to immunotherapy and longer survival in first-line therapy compared with conventional chemotherapy. PD-L1, whose expression is evaluated by using immunohistochemistry analysis, is currently the only biomarker approved for clinical use in the first- and second-line monotherapy setting and therefore plays a central role in treatment decision-making for patients with advanced NSCLC. In this review we will discuss the key role of PD-L1 as a predictive biomarker of response to pembrolizumab therapy in NSCLC patients by describing the appropriate techniques and methodologies for immunohistochemical evaluation of PD-L1 expression and providing an overview of the clinical studies supporting its predictive significance.

Keywords: Checkpoint inhibitors; Lung cancer; NSCLC; PD-1; PD-L1; Pembrolizumab; Predictive biomarker.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents, Immunological / therapeutic use*
  • B7-H1 Antigen / immunology*
  • Biomarkers
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Molecular Targeted Therapy
  • Neoplasm Staging
  • Prognosis
  • Programmed Cell Death 1 Receptor / immunology*
  • Survival Analysis
  • T-Lymphocytes / drug effects

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • Biomarkers
  • Programmed Cell Death 1 Receptor
  • pembrolizumab

Associated data

  • figshare/10.6084/m9.figshare.9135527