Case Report: A patient with the rare third-generation TKI-resistant mutation EGFR L718Q who responded to afatinib plus cetuximab combination therapy

Guoqing Zhang; Beibei Yan; Yanan Guo; Hang Yang; Xiangnan Li; Jindong Li

doi:10.3389/fonc.2022.995624

Case Report: A patient with the rare third-generation TKI-resistant mutation EGFR L718Q who responded to afatinib plus cetuximab combination therapy

Front Oncol. 2022 Oct 31:12:995624. doi: 10.3389/fonc.2022.995624. eCollection 2022.

Authors

Guoqing Zhang¹, Beibei Yan¹, Yanan Guo¹, Hang Yang¹, Xiangnan Li¹, Jindong Li¹

Affiliation

¹ Department of Thoracic Surgery and Lung Transplantation, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Abstract

Third-generation tyrosine kinase inhibitors (TKIs), such as osimertinib, almonertinib and furmonertinib, overcome the mechanisms of resistance to first-generation inhibitors (such as gefitinib, erlotinib and icotinib) by incorporating an acrylamide group that alkylates the Cys797 of EGFR T790M. However, drug resistance is inevitable, even for third-generation TKIs. Screening for drug-resistant mutations by repeat biopsy and repeat gene sequencing is necessary after TKI treatment. Among various third-generation TKI-resistant mutations, secondary mutation of the L718 residue of EGFR exon 18 was found in approximately 8% of patients and is responsible for drug resistance in vitro and in vivo. Furthermore, there is limited clinical experience of targeted therapy for this mutation. Herein, we report for the first time that afatinib and cetuximab combination therapy can overcome such drug resistance.

Keywords: EGFR; L718Q; afatinib; cetuximab; drug resistance; lung adenocarcinoma.

Publication types

Case Reports