Role of Immune Checkpoint Inhibitor Therapy in Advanced EGFR-Mutant Non-Small Cell Lung Cancer

Over the last decade, the treatment of advanced non-small cell lung cancer (NSCLC) has undergone rapid changes with innovations in oncogene-directed therapy and immune checkpoint inhibitors. In patients with epidermal growth factor receptor (EGFR) gene mutant (EGFRm) NSCLC, newer-generation tyrosine...

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Autores principales:	Nathaniel Wiest, Umair Majeed, Karan Seegobin, Yujie Zhao, Yanyan Lou, Rami Manochakian
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Non-small cell lung cancer lung cancer EGFR tyrosine kinase inhibitor immune-mediated adverse effects immune checkpoint inhibitor (ICI) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/8a8afaf9374b4c2f8f1ca6eb45e8a49c
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spelling	oai:doaj.org-article:8a8afaf9374b4c2f8f1ca6eb45e8a49c2021-11-16T04:30:19ZRole of Immune Checkpoint Inhibitor Therapy in Advanced EGFR-Mutant Non-Small Cell Lung Cancer2234-943X10.3389/fonc.2021.751209https://doaj.org/article/8a8afaf9374b4c2f8f1ca6eb45e8a49c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.751209/fullhttps://doaj.org/toc/2234-943XOver the last decade, the treatment of advanced non-small cell lung cancer (NSCLC) has undergone rapid changes with innovations in oncogene-directed therapy and immune checkpoint inhibitors. In patients with epidermal growth factor receptor (EGFR) gene mutant (EGFRm) NSCLC, newer-generation tyrosine kinase inhibitors (TKIs) are providing unparalleled survival benefit and tolerability. Unfortunately, most patients will experience disease progression and thus an urgent need exists for improved subsequent lines of therapies. The concurrent revolution in immune checkpoint inhibitor (ICI) therapy is providing novel treatment options with improved clinical outcomes in wild-type EGFR (EGFRwt) NSCLC; however, the application of ICI therapy to advanced EGFRm NSCLC patients is controversial. Early studies demonstrated the inferiority of ICI monotherapy to EGFR TKI therapy in the first line setting and inferiority to chemotherapy in the second line setting. Additionally, combination ICI and EGFR TKI therapies have demonstrated increased toxicities, and EGFR TKI therapy given after first-line ICI therapy has been correlated with severe adverse events. Nonetheless, combination therapies including dual-ICI blockade and ICI, chemotherapy, and angiogenesis inhibitor combinations are areas of active study with some intriguing signals in preliminary studies. Here, we review previous and ongoing clinical studies of ICI therapy in advanced EGFRm NSCLC. We discuss advances in understanding the differences in the tumor biology and tumor microenvironment (TME) of EGFRm NSCLC tumors that may lead to novel approaches to enhance ICI efficacy. It is our goal to equip the reader with a knowledge of current therapies, past and current clinical trials, and active avenues of research that provide the promise of novel approaches and improved outcomes for patients with advanced EGFRm NSCLC.Nathaniel WiestUmair MajeedKaran SeegobinYujie ZhaoYanyan LouRami ManochakianFrontiers Media S.A.articleNon-small cell lung cancerlung cancerEGFRtyrosine kinase inhibitorimmune-mediated adverse effectsimmune checkpoint inhibitor (ICI)Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Non-small cell lung cancer lung cancer EGFR tyrosine kinase inhibitor immune-mediated adverse effects immune checkpoint inhibitor (ICI) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Non-small cell lung cancer lung cancer EGFR tyrosine kinase inhibitor immune-mediated adverse effects immune checkpoint inhibitor (ICI) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Nathaniel Wiest Umair Majeed Karan Seegobin Yujie Zhao Yanyan Lou Rami Manochakian Role of Immune Checkpoint Inhibitor Therapy in Advanced EGFR-Mutant Non-Small Cell Lung Cancer
description	Over the last decade, the treatment of advanced non-small cell lung cancer (NSCLC) has undergone rapid changes with innovations in oncogene-directed therapy and immune checkpoint inhibitors. In patients with epidermal growth factor receptor (EGFR) gene mutant (EGFRm) NSCLC, newer-generation tyrosine kinase inhibitors (TKIs) are providing unparalleled survival benefit and tolerability. Unfortunately, most patients will experience disease progression and thus an urgent need exists for improved subsequent lines of therapies. The concurrent revolution in immune checkpoint inhibitor (ICI) therapy is providing novel treatment options with improved clinical outcomes in wild-type EGFR (EGFRwt) NSCLC; however, the application of ICI therapy to advanced EGFRm NSCLC patients is controversial. Early studies demonstrated the inferiority of ICI monotherapy to EGFR TKI therapy in the first line setting and inferiority to chemotherapy in the second line setting. Additionally, combination ICI and EGFR TKI therapies have demonstrated increased toxicities, and EGFR TKI therapy given after first-line ICI therapy has been correlated with severe adverse events. Nonetheless, combination therapies including dual-ICI blockade and ICI, chemotherapy, and angiogenesis inhibitor combinations are areas of active study with some intriguing signals in preliminary studies. Here, we review previous and ongoing clinical studies of ICI therapy in advanced EGFRm NSCLC. We discuss advances in understanding the differences in the tumor biology and tumor microenvironment (TME) of EGFRm NSCLC tumors that may lead to novel approaches to enhance ICI efficacy. It is our goal to equip the reader with a knowledge of current therapies, past and current clinical trials, and active avenues of research that provide the promise of novel approaches and improved outcomes for patients with advanced EGFRm NSCLC.
format	article
author	Nathaniel Wiest Umair Majeed Karan Seegobin Yujie Zhao Yanyan Lou Rami Manochakian
author_facet	Nathaniel Wiest Umair Majeed Karan Seegobin Yujie Zhao Yanyan Lou Rami Manochakian
author_sort	Nathaniel Wiest
title	Role of Immune Checkpoint Inhibitor Therapy in Advanced EGFR-Mutant Non-Small Cell Lung Cancer
title_short	Role of Immune Checkpoint Inhibitor Therapy in Advanced EGFR-Mutant Non-Small Cell Lung Cancer
title_full	Role of Immune Checkpoint Inhibitor Therapy in Advanced EGFR-Mutant Non-Small Cell Lung Cancer
title_fullStr	Role of Immune Checkpoint Inhibitor Therapy in Advanced EGFR-Mutant Non-Small Cell Lung Cancer
title_full_unstemmed	Role of Immune Checkpoint Inhibitor Therapy in Advanced EGFR-Mutant Non-Small Cell Lung Cancer
title_sort	role of immune checkpoint inhibitor therapy in advanced egfr-mutant non-small cell lung cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/8a8afaf9374b4c2f8f1ca6eb45e8a49c
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Role of Immune Checkpoint Inhibitor Therapy in Advanced EGFR-Mutant Non-Small Cell Lung Cancer

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