PD-L1 expression and response to pembrolizumab in patients with EGFR-mutant non-small cell lung cancer

Jpn J Clin Oncol. 2020 May 5;50(5):617-622. doi: 10.1093/jjco/hyaa033.

Abstract

Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer is less likely to express programmed death-ligand 1 (PD-L1) than tumors with wild-type EGFR and is associated with poor response to pembrolizumab. To understand the relationship between EGFR mutation and PD-L1 expression in pembrolizumab response, we retrospectively evaluated the factors contributing to the high tumor proportion score in 155 EGFR-mutant non-small cell lung cancer cases and their associated response to pembrolizumab. Uncommon EGFR mutations were significantly associated with a PD-L1 tumor proportion score ≥ 50% compared to common EGFR mutations. The objective response rate to pembrolizumab of 14 patients was 36%, including 22% in patients with common EGFR mutations, 60% in patients with uncommon EGFR mutations and 75% in patients with both uncommon mutations and a PD-L1 tumor proportion score ≥ 50%. A PD-L1 tumor proportion score ≥ 50% was more frequent in non-small cell lung cancer patients harboring uncommon EGFR mutations and was associated with pembrolizumab efficacy.

Keywords: EGFR mutation; non-small cell lung cancer; pembrolizumab; programmed death-ligand 1.

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • B7-H1 Antigen / genetics*
  • B7-H1 Antigen / metabolism
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • B7-H1 Antigen
  • CD274 protein, human
  • pembrolizumab
  • EGFR protein, human
  • ErbB Receptors