Rare mutations of epidermal growth factor receptor in epidermal growth factor receptor-tyrosine kinase inhibitor-naive non-small cell lung carcinoma and the response to erlotinib therapy
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Date
2020-04
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Wolters Kluwer India Pvt. Ltd.
Abstract
Context: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are considered to be effective treatments for advanced NSCLC patients with sensitizing EGFR mutations. There are many complex and rare mutations in the EGFR gene. The efficacy of the first-generation EGFR-TKI (erlotinib) is unknown for tumors harboring rare EGFR mutations. Aims: The purpose of this study was to investigate the clinical significance of rare EGFR mutations in EGFR-TKI-naive patients and the efficacy of erlotinib. Settings and Design: Istanbul University, Istanbul Medical Faculty, Department of Medical Oncology, Istanbul/Turkey, and retrospective observational study. Subjects and Methods: We retrospectively analyzed 117 non-small cell lung cancer (NSCLC) patients with EGFR mutations who had not previously used EGFR-TKIs. Exons 18–21 of EGFR were analyzed by polymerase chain reaction and subjected to direct sequencing methods. Statistical Analysis Used: Survival estimates were calculated by the Kaplan–Meier method using SPSS 25 software (IBM SPSS, Chicago, USA). Results: Of 117 patients who had EGFR mutations, 23 patients had rare and complex EGFR mutations. Only 9 of them were treated with erlotinib. Three patients (3.5%) with exon 20 mutations received erlotinib. Two with EGFR-p. Q787Q (SNP ID, rs10251977; c.2361G>A) synonymous mutation in exon 20 were responsive to erlotinib therapy in the second-line setting after first-line chemotherapy. To the best of our knowledge, the present two cases are the first to be reported with lung adenocarcinoma with EGFR-p. Q787Q synonymous mutation responding to erlotinib. Conclusion: NSCLC patients harboring rare EGFR mutations generally did not show consistent or favorable responses to EGFR-TKI. We suggest that this rare synonymous mutation (EGFR-p. Q787Q) is a sensitive EGFR mutation in NSCLC
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Keywords
Epidermal growth factor receptor mutation, epidermal growth factor receptor‑p.Q787Q, erlotinib, G719C/A, L861Q, non‑small cell lung cancer, S768I
Citation
Sari Murat, Aydiner Adnan. Rare mutations of epidermal growth factor receptor in epidermal growth factor receptor-tyrosine kinase inhibitor-naive non-small cell lung carcinoma and the response to erlotinib therapy. Journal of Cancer Research and Therapeutics. 2020 Apr; 16(1): 132-138