Spotlight on Trastuzumab Deruxtecan (DS-8201,T-DXd) for HER2 Mutation Positive Non-Small Cell Lung Cancer

Ibrahim Azar,1 Samer Alkassis,2 Jami Fukui,3 Fares Alsawah,1 Kalub Fedak,1 Mohammed Najeeb Al Hallak,1 Ammar Sukari,1 Misako Nagasaka1,4 1Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, Detroit, MI, USA; 2Department of Internal Medicine, Wayne State Univ...

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Autores principales:	Azar I, Alkassis S, Fukui J, Alsawah F, Fedak K, Al Hallak MN, Sukari A, Nagasaka M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	t-dxd ds8201 antibody drug conjugate her2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/9ba692e93b22421a822fe42d64c14f13
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spelling	oai:doaj.org-article:9ba692e93b22421a822fe42d64c14f132021-12-02T16:59:45ZSpotlight on Trastuzumab Deruxtecan (DS-8201,T-DXd) for HER2 Mutation Positive Non-Small Cell Lung Cancer1179-2728https://doaj.org/article/9ba692e93b22421a822fe42d64c14f132021-10-01T00:00:00Zhttps://www.dovepress.com/spotlight-on-trastuzumab-deruxtecan-ds-8201t-dxd-for-her2-mutation-pos-peer-reviewed-fulltext-article-LCTThttps://doaj.org/toc/1179-2728Ibrahim Azar,1 Samer Alkassis,2 Jami Fukui,3 Fares Alsawah,1 Kalub Fedak,1 Mohammed Najeeb Al Hallak,1 Ammar Sukari,1 Misako Nagasaka1,4 1Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, Detroit, MI, USA; 2Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI, USA; 3University of Hawaii Manoa Cancer Center, John A. Burns School of Medicine, Honolulu, HI, USA; 4Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, JapanCorrespondence: Misako NagasakaDepartment of Oncology, Karmanos Cancer Center/Wayne State University, Detroit, MI, USATel +1313-576-8772Fax +1313-576-8699Email nagasakm@hs.uci.eduAbstract: Human epidermal growth factor receptor 2 (HER2) is a proto-oncogene that, when mutated or overexpressed, plays an important role in oncogenesis. The landscape of HER2-positive breast cancer has changed dramatically over the past 2 decades with the FDA approval of a growing number of agents (antibodies, tyrosine kinase inhibitors, and antibody-drug conjugates) targeting the HER2 receptor. HER2 inhibition has also been approved for HER2-positive gastric cancer. HER2 is amplified in 9% and mutated in 3% of lung cancer. Historically, HER2-targeted therapy for lung cancer with trastuzumab, pertuzumab, and trastuzumab emtansine has failed to demonstrate a survival benefit. Trastuzumab deruxtecan (T-DXd) is a novel antibody–drug conjugate with a tetrapeptide linker, which delivers a topoisomerase I inhibitor with a drug-to-antibody ratio of 7∼ 8. The potency of the active payload, as well as its significant bystander effect, resulted in significant anti-tumor activity. The DESTINY-Lung01 trial evaluated T-DXd in HER2-positive non-squamous non-small cell lung cancer (NSCLC) and reported a progression-free survival of 14 months in HER2-mutated NSCLC, earning its breakthrough designation by the FDA. In this review, we will discuss the structural characteristics, pharmacodynamics, and pharmacokinetics of T-DXd. We will also shed light on the preclinical and ongoing clinical trials of T-DXd along with future directions in the management of HER2 positive lung cancer.Keywords: T-DXd, DS8201, antibody drug conjugate, HER2Azar IAlkassis SFukui JAlsawah FFedak KAl Hallak MNSukari ANagasaka MDove Medical Pressarticlet-dxdds8201antibody drug conjugateher2Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENLung Cancer: Targets and Therapy, Vol Volume 12, Pp 103-114 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	t-dxd ds8201 antibody drug conjugate her2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	t-dxd ds8201 antibody drug conjugate her2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Azar I Alkassis S Fukui J Alsawah F Fedak K Al Hallak MN Sukari A Nagasaka M Spotlight on Trastuzumab Deruxtecan (DS-8201,T-DXd) for HER2 Mutation Positive Non-Small Cell Lung Cancer
description	Ibrahim Azar,1 Samer Alkassis,2 Jami Fukui,3 Fares Alsawah,1 Kalub Fedak,1 Mohammed Najeeb Al Hallak,1 Ammar Sukari,1 Misako Nagasaka1,4 1Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, Detroit, MI, USA; 2Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI, USA; 3University of Hawaii Manoa Cancer Center, John A. Burns School of Medicine, Honolulu, HI, USA; 4Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, JapanCorrespondence: Misako NagasakaDepartment of Oncology, Karmanos Cancer Center/Wayne State University, Detroit, MI, USATel +1313-576-8772Fax +1313-576-8699Email nagasakm@hs.uci.eduAbstract: Human epidermal growth factor receptor 2 (HER2) is a proto-oncogene that, when mutated or overexpressed, plays an important role in oncogenesis. The landscape of HER2-positive breast cancer has changed dramatically over the past 2 decades with the FDA approval of a growing number of agents (antibodies, tyrosine kinase inhibitors, and antibody-drug conjugates) targeting the HER2 receptor. HER2 inhibition has also been approved for HER2-positive gastric cancer. HER2 is amplified in 9% and mutated in 3% of lung cancer. Historically, HER2-targeted therapy for lung cancer with trastuzumab, pertuzumab, and trastuzumab emtansine has failed to demonstrate a survival benefit. Trastuzumab deruxtecan (T-DXd) is a novel antibody–drug conjugate with a tetrapeptide linker, which delivers a topoisomerase I inhibitor with a drug-to-antibody ratio of 7∼ 8. The potency of the active payload, as well as its significant bystander effect, resulted in significant anti-tumor activity. The DESTINY-Lung01 trial evaluated T-DXd in HER2-positive non-squamous non-small cell lung cancer (NSCLC) and reported a progression-free survival of 14 months in HER2-mutated NSCLC, earning its breakthrough designation by the FDA. In this review, we will discuss the structural characteristics, pharmacodynamics, and pharmacokinetics of T-DXd. We will also shed light on the preclinical and ongoing clinical trials of T-DXd along with future directions in the management of HER2 positive lung cancer.Keywords: T-DXd, DS8201, antibody drug conjugate, HER2
format	article
author	Azar I Alkassis S Fukui J Alsawah F Fedak K Al Hallak MN Sukari A Nagasaka M
author_facet	Azar I Alkassis S Fukui J Alsawah F Fedak K Al Hallak MN Sukari A Nagasaka M
author_sort	Azar I
title	Spotlight on Trastuzumab Deruxtecan (DS-8201,T-DXd) for HER2 Mutation Positive Non-Small Cell Lung Cancer
title_short	Spotlight on Trastuzumab Deruxtecan (DS-8201,T-DXd) for HER2 Mutation Positive Non-Small Cell Lung Cancer
title_full	Spotlight on Trastuzumab Deruxtecan (DS-8201,T-DXd) for HER2 Mutation Positive Non-Small Cell Lung Cancer
title_fullStr	Spotlight on Trastuzumab Deruxtecan (DS-8201,T-DXd) for HER2 Mutation Positive Non-Small Cell Lung Cancer
title_full_unstemmed	Spotlight on Trastuzumab Deruxtecan (DS-8201,T-DXd) for HER2 Mutation Positive Non-Small Cell Lung Cancer
title_sort	spotlight on trastuzumab deruxtecan (ds-8201,t-dxd) for her2 mutation positive non-small cell lung cancer
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/9ba692e93b22421a822fe42d64c14f13
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Spotlight on Trastuzumab Deruxtecan (DS-8201,T-DXd) for HER2 Mutation Positive Non-Small Cell Lung Cancer

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