Abstract

BackgroundTreatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is the standard therapy for advanced non-small cell lung cancer (NSCLC) with common EGFR mutations. However, the efficacy of EGFR-TKIs in patients with uncommon EGFR mutations remains unclear. MethodsWe retrospectively surveyed a consecutive database of patients with NSCLC with EGFR mutations. We analyzed the data of patients with NSCLC with uncommon mutations, including single or compound mutations, who were treated with EGFR-TKIs between May 2016 and October 2018. ResultsData from 543 patients were collected from five institutions, among whom 23 had EGFR uncommon mutations. Twenty-one patients who were treated with any EGFR-TKIs were analyzed in this study, 18 of whom were treated with EGFR-TKIs as first-line therapy (gefitinib 5, erlotinib 3, afatinib 10 patients). In contrast, three patients underwent cytotoxic chemotherapy as first-line therapy and were treated with EGFR-TKIs as second- and third-line therapy (gefitinib 1, erlotinib 1, afatinib 1 patient). According to the Response Evaluation Criteria in Solid Tumors, the overall response rate was 56%, and the disease control rate was 78%. The median progression-free survival (PFS) was 14.0 months in all patients with uncommon mutations. The median PFS of patients who were treated with first and second generation EGFR-TKIs were 14.0 months (n = 10) and 7.3 months (n = 11), respectively. Moreover, the PFS of patients with the G719X mutation (n = 12, median PFS: 32.9 months) was longer than that of patients with the L861Q mutation (n = 4, median PFS: 11.1) and compound mutations (n = 4, median PFS 7.3 months). ConclusionsFirst and second generation EGFR-TKIs are effective treatments for patients with NSCLC with uncommon mutations. Notably, a greater favorable response was observed in patients with G719X mutations than those with L861Q and compound mutations. Clinical trial identificationUMIN000028989. Legal entity responsible for the studyFumio Imamura. FundingAstraZeneca. DisclosureF. Imamura: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca. All other authors have declared no conflicts of interest.

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