Papers

International journal
2019

Retrospective analysis of antitumor effects and biomarkers for nivolumab in NSCLC patients with EGFR mutations.

PloS one
  • Miyuki Sato
  • ,
  • Satoshi Watanabe
  • ,
  • Hiroshi Tanaka
  • ,
  • Koichiro Nozaki
  • ,
  • Masashi Arita
  • ,
  • Miho Takahashi
  • ,
  • Satoshi Shoji
  • ,
  • Kosuke Ichikawa
  • ,
  • Rie Kondo
  • ,
  • Nobumasa Aoki
  • ,
  • Masachika Hayashi
  • ,
  • Yasuyoshi Ohshima
  • ,
  • Toshiyuki Koya
  • ,
  • Riuko Ohashi
  • ,
  • Yoichi Ajioka
  • ,
  • Toshiaki Kikuchi

Volume
14
Number
4
First page
e0215292
Last page
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1371/journal.pone.0215292

Although the blockade of programmed cell death 1 (PD-1)/PD-ligand (L) 1 has demonstrated promising and durable clinical responses for non-small-cell lung cancers (NSCLCs), NSCLC patients with epidermal growth factor receptor (EGFR) mutations responded poorly to PD-1/PD-L1 inhibitors. Previous studies have identified several predictive biomarkers, including the expression of PD-L1 on tumor cells, for PD-1/PD-L1 blockade therapies in NSCLC patients; however, the usefulness of these biomarkers in NSCLCs with EGFR mutations has not been elucidated. The present study was conducted to evaluate the predictive biomarkers for PD-1/PD-L1 inhibitors in EGFR-mutated NSCLCs. We retrospectively analyzed 9 patients treated with nivolumab for EGFR-mutated NSCLCs. All but one patient received EGFR-tyrosine kinase inhibitors before nivolumab treatment. The overall response rate and median progression-free survival were 11% and 33 days (95% confidence interval (CI); 7 to 51), respectively. Univariate analysis revealed that patients with a good performance status (P = 0.11; hazard ratio (HR) 0.183, 95% CI 0.0217 to 1.549), a high density of CD4+ T cells (P = 0.136; HR 0.313, 95% CI 0.045 to 1.417) and a high density of Foxp3+ cells (P = 0.09; HR 0.264, 95% CI 0.0372 to 1.222) in the tumor microenvironment tended to have longer progression-free survival with nivolumab. Multivariate analysis revealed that a high density of CD4+ T cells (P = 0.005; HR<0.001, 95% CI <0.001 to 0.28) and a high density of Foxp3+ cells (P = 0.003; HR<0.001, 95% CI NA) in tumor tissues were strongly correlated with better progression-free survival. In contrast to previous studies in wild type EGFR NSCLCs, PD-L1 expression was not associated with the clinical benefit of anti-PD-1 treatment in EGFR-mutated NSCLCs. The current study indicated that immune status in the tumor microenvironment may be important for the effectiveness of nivolumab in NSCLC patients with EGFR mutations.

Link information
DOI
https://doi.org/10.1371/journal.pone.0215292
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30978241
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461262
ID information
  • DOI : 10.1371/journal.pone.0215292
  • Pubmed ID : 30978241
  • Pubmed Central ID : PMC6461262

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