Breaking the biomarker code: PD-L1 expression and checkpoint inhibition in advanced NSCLC Academic Article uri icon

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  • 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.


  • Melosky, B
  • Chu, Q
  • Juergens, Rosalyn
  • Leighl, N
  • Ionescu, D
  • Tsao, M-S
  • McLeod, D
  • Hirsh, V

publication date

  • April 2018