Breaking the biomarker code: PD-L1 expression and checkpoint inhibition in advanced NSCLC

Cancer Treat Rev. 2018 Apr;65:65-77. doi: 10.1016/j.ctrv.2018.02.005. Epub 2018 Feb 22.

Abstract

Background: Lung cancer is the most common cause of cancer-related death among males and the second leading cause among females globally. Checkpoint inhibitors re-engage the immune system to fight cancer. This review evaluates phase III data on the use of checkpoint inhibitors in the treatment of advanced NSCLC and addresses PD-L1 expression in predicting efficacy.

Methods: Six phase III clinical trials investigating checkpoint inhibitors for NSCLC were identified through a search of PubMed (to November 15, 2016) and conference databases, with findings updated from a directed search of eligible studies conducted in January 2018.

Results: Significant reductions in the risk of death ranging from 27% to 41% and were observed second-line and beyond. A relationship between PD-L1 expression and survival was apparent in most trials with optimal benefit for the highest expression levels (≥50%). Benefit was also observed at low or no PD-L1 expression levels and in third-line in some studies. Significantly improved PFS was observed for pembrolizumab at high PD-L1 expression levels (≥50%) first-line. Immune-related adverse events associated with checkpoint inhibitors are tolerable and rates of pneumonitis may be lower among PD-L1 inhibitors. Use of checkpoint inhibitors for tumors with driver mutations should only be considered after all appropriate targeted therapy and chemotherapy have been exhausted. PD-L1 testing presents a valuable tool to guide treatment sequencing and we recommend use of agent-specific PD-L1 tests and respective scoring systems until a standardized, convenient and broadly applicable test is identified.

Conclusions: Checkpoint inhibitors represent a major advance in the treatment of advanced NSCLC and PD-L1 status can inform treatment decisions.

Keywords: Biomarkers; Checkpoint inhibitors; Lung cancer; NSCLC; PD-L1.

Publication types

  • Review

MeSH terms

  • B7-H1 Antigen / antagonists & inhibitors*
  • B7-H1 Antigen / biosynthesis*
  • B7-H1 Antigen / immunology
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / immunology
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Clinical Trials, Phase III as Topic
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology*
  • Molecular Targeted Therapy
  • Randomized Controlled Trials as Topic

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human