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Review
. 2022 Feb;7(1):100395.
doi: 10.1016/j.esmoop.2022.100395. Epub 2022 Feb 8.

Consensus for HER2 alterations testing in non-small-cell lung cancer

S Ren  1 , J Wang  2 , J Ying  2 , T Mitsudomi  3 , D H Lee  4 , Z Wang  2 , Q Chu  5 , P C Mack  6 , Y Cheng  7 , J Duan  2 , Y Fan  8 , B Han  9 , Z Hui  10 , A Liu  11 , J Liu  12 , Y Lu  13 , Z Ma  14 , M Shi  15 , Y Shu  16 , Q Song  17 , X Song  18 , Y Song  19 , C Wang  20 , X Wang  21 , Z Wang  22 , Y Xu  23 , Y Yao  24 , L Zhang  25 , M Zhao  26 , B Zhu  27 , J Zhang  28 , C Zhou  29 , F R Hirsch  6
Affiliations
Review

Consensus for HER2 alterations testing in non-small-cell lung cancer

S Ren et al. ESMO Open. 2022 Feb.

Erratum in

Abstract

Human epidermal growth factor receptor 2 (HER2) is a transmembrane glycoprotein receptor with intracellular tyrosine kinase activity. Its alterations, including mutation, amplification and overexpression, could result in oncogenic potential and have been detected in many cancers such as non-small-cell lung cancer (NSCLC). Such alterations are, in general, considered markers of poor prognosis. Anti-HER2 antibody-drug conjugates, e.g. trastuzumab deruxtecan (T-DXd, DS-8201) and disitamab vedotin (RC48), were recently approved for HER2-positive breast and gastric cancers. Meanwhile, several HER2-targeted drugs, such as T-DXd, neratinib, afatinib, poziotinib and pyrotinib, have been evaluated in patients with advanced NSCLC, with several of them demonstrating clinical benefit. Therefore, identifying HER2 alterations is pivotal for NSCLC patients to benefit from these targeted therapies. Recent guidelines on HER2 testing were developed for breast and gastric cancer, however, and have not been fully established for NSCLC. The expert group here reached a consensus on HER2 alteration testing in NSCLC with the focus on clinicopathologic characteristics, therapies, detection methods and diagnostic criteria for HER2-altered NSCLC patients. We hope this consensus could improve the clinical management of NSCLC patients with HER2 alterations.

Keywords: amplification; gene testing; human epidermal growth factor receptor 2; mutation; non-small-cell lung cancer; overexpression.

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Conflict of interest statement

Disclosure JZ served as a scientific advisor/consultant for AstraZeneca, Biodesix, Novocure, Bayer, Daiichi Sankyo, Mirati, Novartis, Cardinal Health, Bristol Myers Squibb, Nexus Health and Sanofi, is on the speakers’ bureau for AstraZeneca and MJH Life Sciences and has received research funding from AstraZeneca, Biodesix, Novartis, Genentech/Roche, Mirati, AbbVie and Hengrui Therapeutics. FRH participated in scientific advisory boards for: Bristol Myers Squibb, Genentech, Merck, Novartis, AstraZeneca/Daiichi, Sanofi/Regeneron, OncoCyte. CZ reported honoraria as a speaker from Roche, Lily China, Boehringer Ingelheim, Merck, Hengrui, Qilu, Sanofi, Merck Sharp & Dohme, Innovent Biologics, C-Stone, Luye Pharma, TopAlliance Biosciences, and Amoy Diagnositics; and advisor fees for Innovent Biologics, Hengrui, Qilu, and TopAlliance Biosciences. SR reported honoraria as a speaker from Boehringer Ingelheim, Lilly, Merck Sharp & Dohme, Roche, Hengrui, and Junshi, advisor fees for Roche, Merck Sharp & Dohme, and Boehringer Ingelheim and research funding from Hengrui. All other authors have declared no conflicts of interest.

Figures

Figure 1
Figure 1
Recommended algorithm for testing HER2 alterations in non-small-cell lung cancer. The definitions of HER2 expression and amplification in this consensus were determined based on available clinical studies; further verification is recommended when HER2 amplification is detected by NGS or PCR. ctDNA, circulating tumor DNA; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; NGS, next-generation sequencing.
See this image and copyright information in PMC

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