Background: T790M mutation is well known as the most common mechanism for resistance to the first- and second-generation tyrosine kinase inhibitors (TKIs) for EGFR mutation in non-small-cell lung cancer. Several third-generation EGFR TKIs, such as osimertinib, have been explored and approved for conquering this resistance; however, acquired resistance to osimertinib is evident and the resistance mechanisms remain complex and incompletely explored.
Case Presentation: A non-smoking 58-year-old female patient was initially diagnosed with lung adenocarcinoma harboring EGFR exon 19 deletion and clinically responded to initial gefitinib treatment. The patient progressed on gefitinib after >1 year and a T790M mutation was detected in tissue biopsy by next-generation sequencing (NGS). Osimertinib treatment was administrated for several months and an acquired rare EGFR G724S mutation was detected via NGS blood sample after osimertinib resistance.
Conclusion: The specific mechanisms of acquiring drug resistance for EGFR-TKIs have not been fully explored. EGFR G724S mutation might be associated with osimertinib resistance but more studies about the mechanism should be explored.
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http://dx.doi.org/10.2147/OTT.S188612 | DOI Listing |
Onco Targets Ther
May 2024
Pulmonology Department, Créteil Intercommunal Hospital, Créteil, France.
Transl Lung Cancer Res
April 2024
Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China.
Background: Somatic mutations in epidermal growth factor receptor () exon 18 are classified as uncommon or rare mutations in non-small cell lung cancer (NSCLC), in this context, other than G719X or E709X exon 18 mutations are even more rare and heterogeneous. In such scenario, first line treatment options are still debated. The aim of this study was to investigate the response of NSCLC patients harboring very rare exon 18 mutations to EGFR tyrosine kinase inhibitors (EGFR-TKIs).
View Article and Find Full Text PDFFront Oncol
November 2022
Department of Medical Oncology of Respiratory, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China.
G724S mutation in exon 18 has been shown to be resistant to both first- and third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, we found a rare mutation of Ex19del/G724S in two patients with lung cancer who demonstrated a favorable response to the combination of afatinib and chemotherapy. Identified by next-generation sequencing (NGS), G724S was found from a primary and a secondary tumor biopsy, respectively.
View Article and Find Full Text PDFInvest New Drugs
December 2022
Division of Respiratory Medicine, Mito Medical Center, University of Tsukuba, 3-2-7 Miya-machi, 310-0105, Mito, Ibaraki, Japan.
Recently, we read a paper "Dacomitinib overcomes afatinib-refractory carcinomatous meningitis in a lung cancer patient harbouring EGFR Ex.19 deletion and G724S mutation" published in Investigational New Drugs. Their patient had a very rare compound EGFR mutation.
View Article and Find Full Text PDFAnticancer Drugs
October 2022
Department of Medical Oncology, University Hospital of Udine, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC).
Epidermal growth factor receptor (EGFR) G724S mutation represents a resistance mechanism to first- and third-generation EGFR tyrosine kinase inhibitors. Limited data are available regarding the efficacy of afatinib in patients with non-small cell lung cancer (NSCLC) harboring G724S mutation, particularly after osimertinib. A patient diagnosed with advanced EGFR-mutated (exon 19 deletion) NSCLC after several lines of treatment - gefitinib, osimertinib, heat shock protein inhibitors and chemotherapy-developed EGFR G724S mutation retaining the exon 19 deletion.
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