The association between PD-L1 and EGFR status and the prognostic value of PD-L1 in advanced non-small cell lung cancer patients treated with EGFR-TKIs

Oncotarget. 2015 Jun 10;6(16):14209-19. doi: 10.18632/oncotarget.3694.


Backgrounds: Recent clinical trials have shown that immune-checkpoint blockade yields remarkable response in a subset of non-small cell lung cancer (NSCLC) patients. However, few studies directly focus on the association between epidermal growth factor receptor (EGFR) mutational status and programmed cell death-ligand 1 (PD-L1) expression. We examined whether PD-L1 is related to clinicopathologic factors and prognosis in patients with advanced NSCLC treated with EGFR-tyrosine kinase inhibitors (EGFR-TKIs).

Methods: One-hundred and seventy patients with advanced NSCLC were explored. Paraffin-embedded tumour sections were stained with PD-L1 antibody. EGFR mutation was examined by fluorescent quantitative polymerase chain reaction (PCR). The correlations between PD-L1 expression and EGFR status and survival parameters were analyzed.

Results: The overall frequency of PD-L1 over-expression was 65.9% (112/170). In lung adenocarcinoma, PD-L1 tended to be associated with mutant EGFR (PD-L1 overexpression in mutant and wild-type EGFR, 64/89 (71.9%) vs. 32/56 (57.1%), respectively; p=0.067). Subgroup analyses showed that high PD-L1 expression was associated with significantly shorter overall survival (OS) in EGFR wild-type patients (p=0.029) but not in EGFR mutant patients (p=0.932) treated with EGFR-TKIs. Even more, for EGFR mutant patients, higher expression of PD-L1 might only signal better outcome with TKIs.

Conclusions: High PD-L1 expression was likely to be associated with the presence of EGFR mutation in advanced lung adenocarcinoma. For EGFR wild-type patients, the PD-L1 over expression can be considered as a poor prognostic indicator of OS.

Keywords: EGFR status; NSCLC; PD-L1; TKI; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / biosynthesis*
  • B7-H1 Antigen / genetics
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • ErbB Receptors / biosynthesis*
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Survival Analysis


  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Protein Kinase Inhibitors
  • EGFR protein, human
  • ErbB Receptors