Targeting HER2 in non-small-cell lung cancer (NSCLC) : a glimpse of hope? An updated review on therapeutic strategies in NSCLC harbouring HER2 alterations
Riudavets, M. (Department of Cancer Medicine. Gustave Roussy Cancer Campus)
Sullivan, Ivana (Institut d'Investigació Biomèdica Sant Pau)
Abdayem, P. (Department of Cancer Medicine. Gustave Roussy Cancer Campus)
Planchard, D. (Department of Cancer Medicine. Gustave Roussy Cancer Campus)

Date:	2021
Abstract:	Non-small-cell lung cancer (NSCLC) harbouring HER2 alterations is now considered a distinct molecular subtype. The activation of HER2 in NSCLC occurs via three mechanisms, i. e. gene mutation (1%-4% of cases), gene amplification (2%-5%) and protein overexpression (2%-30%), with different prognostic and predictive outcomes. So far, non-selective tyrosine kinase inhibitors (TKIs) have shown a minor benefit in HER2-mutant NSCLC patients with objective response rates (ORRs) ranging from 0% to 19%. Trastuzumab-based chemotherapy was not found to be superior to chemotherapy alone [median progression-free survival (PFS) 6. 1 versus 7 months, respectively] and dual HER2 antibody blockade with trastuzumab and pertuzumab had limited efficacy (ORR 13%-21%). In contrast, novel more selective HER2 TKIs such as poziotinib and pyrotinib have shown a promising activity in HER2-mutant pre-treated NSCLC patients, with response rates up to 38% and 44%, respectively. The most encouraging data come from phase II studies that evaluated the antibody-drug conjugates (ADCs) ado-trastuzumab-emtansine and trastuzumab-deruxtecan in patients with HER2-mutant NSCLC, with response rates of 50% and 62%, respectively. These agents are bringing hope to the management of HER2-altered NSCLC. Moreover, a paradigm shift from monotherapies towards combinations of agents with distinct mechanisms of action, such as ADCs with irreversible TKIs or immune checkpoint inhibitors, is already taking place and will change the therapeutic landscape of HER2-driven NSCLC. This paper provides a practical, concise and updated review on the therapeutic strategies in NSCLC with HER2 molecular alterations.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article de revisió ; recerca ; Versió publicada
Subject:	Non-small-cell lung cancer ; HER2 mutation ; HER2 amplification ; HER2 overexpression ; Targeted therapies
Published in:	ESMO open, Vol. 6 Núm. 5 (october 2021) , p. 100260, ISSN 2059-7029

DOI: 10.1016/j.esmoop.2021.100260
PMID: 34479034

14 p, 445.0 KB

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