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• W3033658985 abstract "Background: MET amplification is one of the EGFR-independent mechanisms of EGFR tyrosine kinase inhibitor (TKI) resistance. Combinatorial therapy of EGFR-TKI and crizotinib has been explored as a strategy to overcome resistance by simultaneously targeting both EGFR and MET pathways; however, no consensus still exists on the optimal combination regimen with the most benefit.Methods: Retrospective analysis was performed on the clinical and sequencing data obtained from eleven patients with lung adenocarcinoma who acquired MET amplification at progression from prior EGFR-TKI therapy and received a combination of EGFR-TKI and crizotinib.Results: Acquired MET amplification was detected in four and seven patients who progressed from first-line gefitinib and second-line osimertinib, respectively. Six and five patients received a combination of either first-generation (gefitinib, erlotinib, or icotinib) or third-generation (osimertinib) EGFR-TKI and crizotinib, respectively. Nine patients achieved partial response, resulting in an overall response rate of 81.8 %. The median progression-free survival of the cohort was 5.8 months. Moreover, analysis of acquired resistance mechanisms from nine patients identified EGFR T790 M from three patients who progressed from first-generation EGFR-TKI and crizotinib, while EGFR T790 M/trans-C797S and L718Q, EGFR G724S, and CCDC6-RET fusion were detected from one patient each who progressed from osimertinib and crizotinib regimen. Loss of MET amplification was also observed in a majority of the patients at progression from the combination therapy.Conclusions: Our study provides clinical evidence of the efficacy of combinatorial regimen with either first- or third-generation EGFR-TKI and crizotinib after the emergence of MET amplification-mediated EGFR-TKI resistance in patients with EGFR-mutant NSCLC." @default.
• W3033658985 created "2020-06-12" @default.
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• W3033658985 date "2020-08-01" @default.
• W3033658985 modified "2023-10-17" @default.
• W3033658985 title "The clinical efficacy of combinatorial therapy of EGFR-TKI and crizotinib in overcoming MET amplification-mediated resistance from prior EGFR-TKI therapy" @default.
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• W3033658985 doi "https://doi.org/10.1016/j.lungcan.2020.06.003" @default.
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