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Retrospective analysis of antitumor effects and biomarkers for nivolumab in NSCLC patients with EGFR mutations
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 studie...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461262/ https://www.ncbi.nlm.nih.gov/pubmed/30978241 http://dx.doi.org/10.1371/journal.pone.0215292 |
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author | Sato, Miyuki Watanabe, Satoshi Tanaka, Hiroshi Nozaki, Koichiro Arita, Masashi Takahashi, Miho Shoji, Satoshi Ichikawa, Kosuke Kondo, Rie Aoki, Nobumasa Hayashi, Masachika Ohshima, Yasuyoshi Koya, Toshiyuki Ohashi, Riuko Ajioka, Yoichi Kikuchi, Toshiaki |
author_facet | Sato, Miyuki Watanabe, Satoshi Tanaka, Hiroshi Nozaki, Koichiro Arita, Masashi Takahashi, Miho Shoji, Satoshi Ichikawa, Kosuke Kondo, Rie Aoki, Nobumasa Hayashi, Masachika Ohshima, Yasuyoshi Koya, Toshiyuki Ohashi, Riuko Ajioka, Yoichi Kikuchi, Toshiaki |
author_sort | Sato, Miyuki |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6461262 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-64612622019-05-03 Retrospective analysis of antitumor effects and biomarkers for nivolumab in NSCLC patients with EGFR mutations Sato, Miyuki Watanabe, Satoshi Tanaka, Hiroshi Nozaki, Koichiro Arita, Masashi Takahashi, Miho Shoji, Satoshi Ichikawa, Kosuke Kondo, Rie Aoki, Nobumasa Hayashi, Masachika Ohshima, Yasuyoshi Koya, Toshiyuki Ohashi, Riuko Ajioka, Yoichi Kikuchi, Toshiaki PLoS One Research Article 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. Public Library of Science 2019-04-12 /pmc/articles/PMC6461262/ /pubmed/30978241 http://dx.doi.org/10.1371/journal.pone.0215292 Text en © 2019 Sato et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Sato, Miyuki Watanabe, Satoshi Tanaka, Hiroshi Nozaki, Koichiro Arita, Masashi Takahashi, Miho Shoji, Satoshi Ichikawa, Kosuke Kondo, Rie Aoki, Nobumasa Hayashi, Masachika Ohshima, Yasuyoshi Koya, Toshiyuki Ohashi, Riuko Ajioka, Yoichi Kikuchi, Toshiaki Retrospective analysis of antitumor effects and biomarkers for nivolumab in NSCLC patients with EGFR mutations |
title | Retrospective analysis of antitumor effects and biomarkers for nivolumab in NSCLC patients with EGFR mutations |
title_full | Retrospective analysis of antitumor effects and biomarkers for nivolumab in NSCLC patients with EGFR mutations |
title_fullStr | Retrospective analysis of antitumor effects and biomarkers for nivolumab in NSCLC patients with EGFR mutations |
title_full_unstemmed | Retrospective analysis of antitumor effects and biomarkers for nivolumab in NSCLC patients with EGFR mutations |
title_short | Retrospective analysis of antitumor effects and biomarkers for nivolumab in NSCLC patients with EGFR mutations |
title_sort | retrospective analysis of antitumor effects and biomarkers for nivolumab in nsclc patients with egfr mutations |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461262/ https://www.ncbi.nlm.nih.gov/pubmed/30978241 http://dx.doi.org/10.1371/journal.pone.0215292 |
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