Objective:Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-activating mutations have higher response rate and more prolonged survival following treatment with single-agent EGFR tyrosine kinase inhibitor (EGFR-TKI) compared with patients with wild-type EGFR. However, all patients treated with reversible inhibitors develop acquired resistance over time. hTe mechanisms of resistance are complicated. hTe lack of established therapeutic options for patients atfer a failed EGFR-TKI treatment poses a great challenge to physicians in managing this group of lung cancer patients. hTis study evaluates the inlfuence of EGFR-TKI retreatment following chemotherapy atfer failure of initial EGFR-TKI within at least 6 months on NSCLC patients. Methods:hTe data of 27 patients who experienced treatment failure from their initial use of EGFR-TKI within at least 6 months were analyzed. Atfer chemotherapy, the patients were retreated with EGFR-TKI (geiftinib 250 mg qd or erlotinib 150 mg qd), and the tumor progression was observed. The patients were assessed for adverse events and response to therapy. Targeted tumor lesions were assessed with CT scan. Results:Of the 27 patients who received EGFR-TKI retreatment, 1 (3.7%) patient was observed in complete response (CR), 8 (29.6%) patients in partial response (PR), 14 (51.9%) patients in stable disease (SD), and 4 (14.8%) patients in progressive disease (PD). hTe disease control rate (DCR) was 85.2%(95%CI:62%-94%). hTe median progression-free survival (mPFS) was 6 months (95%CI:1-29). Of the 13 patients who received the same EGFR-TKI, 1 patient in CR, 3 patients in PR, 8 patients in SD, and 2 patients in PD were observed. hTe DCR was 84.6%, and the mPFS was 5 months. Of the 14 patients who received another EGFR-TKI, no patient in CR, 6 patients in PR, 6 patients in SD, and 2 patients in PD were observed. hTe DCR was 85.7%, and the mPFS was 9.5 months. Signiifcant difference was found between the two groups in PFS but not in response rate or DCR. Conclusion:Retreatment of EGFR-TKIs can be considered an option atfer failure of chemotherapy for patients who were previously controlled by EGFR-TKI treatment.