Acquired multiple <em>EGFR</em> mutations‑mediated resistance to a third‑generation tyrosine kinase inhibitor in a patient with lung adenocarcinoma who responded to afatinib: A case report and literature review

Yang,Fang; Liu,Jingjing; Xu,Mingming; Peng,Bin

doi:10.3892/ol.2024.14827

Acquired multiple EGFR mutations‑mediated resistance to a third‑generation tyrosine kinase inhibitor in a patient with lung adenocarcinoma who responded to afatinib: A case report and literature review

Authors:
- Fang Yang
- Jingjing Liu
- Mingming Xu
- Bin Peng
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Affiliations: Department of Oncology, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute, Peking University Shenzhen Hospital, Shenzhen‑Peking University‑Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong 518036, P.R. China, Department of Thoracic Surgery, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong 518020, P.R. China
Published online on: November 27, 2024 https://doi.org/10.3892/ol.2024.14827
Article Number: 81
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

For patients with advanced non‑small cell lung cancer (NSCLC) that have epidermal growth factor receptor (EGFR) mutations, EGFR tyrosine kinase inhibitors (TKIs) are the standard treatment and have significant clinical benefits. Third‑generation TKIs, such as osimertinib, almonertinib and furmonertinib, are effective for the treatment of NSCLC that is EGFR‑sensitizing mutation‑positive and T790M‑positive. Despite the efficacy of third‑generation TKIs, patients inevitably develop resistance and the resistance mechanisms are heterogeneous. Second‑generation inhibitors, such as afatinib, may be crucial in treating diseases that have developed resistance to first‑ or third‑generation inhibitors. However, the clinical effect of afatinib in patients with acquired multiple EGFR mutations is not well defined. To the best of our knowledge, the present report describes the first case of a patient with lung adenocarcinoma who had multiple co‑existing EGFR resistance mutations, including EGFR L718Q, EGFR C797S, EGFR C797G, EGFR L792H, EGFR V802F and EGFR V689L. These mutations conferred resistance to almonertinib, whilst maintaining sensitivity to afatinib.

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