Is There a Role for Multiple Lines of Anti-HER2 Therapies Administered Beyond Progression in HER2-Mutated Non-Small Cell Lung Cancer? A Case Report and Literature Review

• Main Authors: Giulio Metro, Sara Baglivo, Riccardo Moretti, Guido Bellezza, Angelo Sidoni, Fausto Roila
• Format: Article
• Language: English
• Published: Adis, Springer Healthcare 2020-07-01
• Series: Oncology and Therapy
• Subjects: Beyond progression; HER2 mutation; Non-small cell lung cancer; Poziotinib; Trastuzumab
• Online Access: https://doi.org/10.1007/s40487-020-00121-5
• ISSN: 2366-1070; 2366-1089

Abstract Oncogene-addicted non-small cell lung cancer (NSCLC) comprises a number of distinct disease subtypes, each of which is characterised by druggable genetic alterations. Among them, the receptor tyrosine kinase protein human epidermal receptor 2 (HER2) is occasionally found deregulated via gene mutation and/or amplification and/or protein overexpression. HER2 mutation, in particular, is a relatively rare condition which occurs in 1–4% of NSCLC patients, especially in those with adenocarcinoma histology and a never/light smoking history. However, the clinical relevance of a HER2 mutation in NSCLC relies on the fact that this genetic alteration has been associated with sensitivity to anti-HER2 therapies such as the monoclonal antibody trastuzumab or the pan-HER-tyrosine kinase inhibitor poziotinib. Here we describe the case of a NSCLC patient with an activating exon 20 G776VinsC mutation in the HER2 gene who responded well to multiple lines of trastuzumab-based therapies administered beyond progression and poziotinib given sequentially. In this specific case, the discovery of a druggable genetic alteration such as a mutation in the HER2 gene allowed for long-term control of the disease through the use of highly effective anti-HER2 therapies.