Introduction The first or second generation EGFR TKI drugs showed good overall response and progression free survival rates in EGFR mutation positive patients. However, most of them progress within 12 months from treatment start due to acquired resistance. In clinical practice, many physicians frequently offer these patients retreatment with EGFR TKIs after a chemotherapy break, because EGFR TKI retreatment can reduce the regrowing EGFR TKI sensitive clones. We evaluated induction of T790M mutation in previously sensitive EGFR mutation positive cancer patients that repeatedly treated EGFR TKIs. Method We reviewed the medical records of patients who were rechallenged with first generation EGFR TKIs. Those patients were previously responded to gefitinib or erlotinib and progressed after several chemotherapies. We analyzed the clincopathological characteristics, treatment modality and their outcome, and development of T790M mutation. EGFR mutations in exons 18, 19, 20, and 21 were evaluated with PNA mediated PCR clamping method. Results Three patients showed acquired T790M mutation after first generation EGFR TKIs retreatment. The acquired T790M mutation was detected in the tumor tissue in two patients and in the bronchoalveolar lavage fluid in the other patient. Three patients were taking osimertinib or olmutinib, two patients showed good clinical efficacy and low adverse events, however the other patient showed serious adverse event (interstitial lung disease). Conclusions Re-treatment with first generation EGFR TKIs after drug holiday in sensitizing EGFR mutant patients are considered to be an effective option, because EGFR TKI retreatment can reduce the regrowing EGFR TKI sensitive clones. Moreover, retreatment of first generation EGFR TKI may also induce or expand EGFR TKI resistance by T790M mutation and it could be treated with third generation EGFR TKI.

Citation Format: Sung Yong Lee, Jee Youn OH, Jae Jeong Shim, Kyung Ho Kang, Kyung Hoon Min. Acquired T790M mutation after first generation EGFR tyrosine kinase retreatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1819.