• Jielin Li, Meizi Jin, Yuzhu Diao, and Xiaoling Li.
• Department of Thoracic Internal Medicine, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China.
• Medicine (Baltimore). 2024 Jul 12; 103 (28): e38789e38789.

RationaleAcquired resistance still inevitably occurs in patients treated with third-generation TKI osimertinib. Although the EGFR L718Q mutation has been reported as a scarce mechanism of osimertinib resistance, advanced therapeutic strategies are still in development. In this report, we included 2 cases of patients who acquired EGFR L858R/L718Q mutation after osimertinib and were overcome by dacomitinib.Patient ConcernsCase 1: A 77-year-old woman was diagnosed with stage IV lung adenocarcinoma. Case 2: A 64-year-old woman was diagnosed with stage IV lung adenocarcinoma.DiagnosesCase 1: The patient was diagnosed with adenocarcinoma with EGFR L858R mutation. Since then, treatment with gefitinib was administrated, leading to a progression-free survival of 18 months. The treatment was switched to osimertinib based on the detection of EGFR T790M mutation, resulting in a progression-free survival of 24 months. Subsequently, EGFR L718Q mutation was detected. Case 2: The patient was diagnosed with adenocarcinoma with EGFR L858R mutation. Icotinib was used as the first-line treatment for 7 months. Osimertinib was applied as the second-line treatment for 13 months based on the EGFR T790M mutation. Subsequently, EGFR L718Q mutation was detected.InterventionsCase 1: Dacomitinib was administered. Case 2: Dacomitinib was administered.OutcomesCase 1:The progression-free survival was 8 months. Case 2: The progression-free survival was 3 months.LessonsDacomitinib is a potential treatment option for NSCLC patients with EGFR L718Q mutation after resistance to Osimertinib. Further research is needed to validate the efficacy of Dacomitinib in this context.Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.

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