CMET-30. BRAIN METASTASES FROM EGFR-MUTATED NSCLC WHICH HAD ACQUIRED RESISTANCE TO EGFR-TKI. ~LESS-FREQUENT T790M AND PRESERVED RESPONSE TO OTHER TKIs

Abstract BACKGROUND Despite the favorable response, most brain metastases (MBs) acquire resistance to TKIs. T790M is the most common mechanism and accounts for approximately half of acquired resistance to TKIs. The aim of this study is to clarify the role of T790M in the acquired resistance of BMs, and optimal treatment for BMs progressed after TKI. METHOD: Upfront TKI was performed for BMs from EGFR-mutated NSCLC, and TKI was changed at progression. Gefitinib, erlotinib, afatinib and osimertinib were used and the selection of these TKIs were owing to the physicians’ decision. During the disease course, re-biopsies of progressed diseases were performed to verify mutations of EGFR, and the incidences of T790M were compared among the organs biopsied. The time to CNS-progression (TCP) were evaluated for each TKI. RESULTS 141 cases were enrolled. Gefitinib was used only as the first line TKI (n=91). Erlotinib was selected for both the gefitinib-naïve patients (n=27) and after gefitinib (n=51). Afatinib (n=21) and osimertinib (n=17) were selected for only recurrent cases. TCPs after gefitnib, erlotinib, afatinib, and osimertinib were 13.4, 20.1, 19.9, and 13.8months, respectively. The history of treatment with gefitinib did not affect the TCP after erlotinib (HR:1.37, 95%CI:0.61–3.25, P=0.451). Re-evaluations of EGFR was performed using 107 samples (lung:51, serum:25, CNS:22, others:9) from 88 cases. The incidence of T790M from CNS samples was 9.1% (Tumor:1/6, CSF:1/16), and was significantly lower than that from the other organs (lung:50.1%, surum:28.0%, others:44.4%) (Odds ratio:0.130, P=0.001). The extremely low incidence of T790M and satisfied effects of TKIs even after TKI-failure suggested the different mechanism of acquired resistance of BMs to TKIs in compared with the extracranial lesions. CONCLUSIONS: T790M played only a limited role in acquired resistance of BMs to TKIs, and alterations of the types of TKIs were still recommended for the progressed BMs after TKI.