晚期非小細胞肺癌EGFR-TKI獲得性耐藥的熱點研究及進展主要內容：EGFR-TKI作用機制、耐藥機制新藥臨床研究前景展望kkkEGFRPPERBB3PPPPAKTKRASJak/StatPEGFR信號傳導的分子機制JkkkEGFRPPPTKIGefitinibErlotinibKRASXJak/StatXAKTXEGFR-TKI作用機制主要內容：EGFR-TKI作用機制、耐藥機制新藥研究前景展望 EGFR-TKI耐藥機制49%5%3%2%11%23%2%3%T790kkkEGFRPERBB3PPAKTKRASJak/StatPT790GefitinibErlotinibT790M介導EGFR-TKI耐藥機制EGFR-TKI耐藥熱點研究梳理EGFR-tki耐藥其他T790突變MET擴增3代TKI2代TKIMET抑制劑TivantinibonartuzmabAfatinibDacomitinibCO1686/AZD9291RR10%PFS小于4mC01686——Rociletinib

RociletinibinEGFR-MutatedNon–Small-CellLungCancer(NCT01526928)N=130TKIARNSCLC

T790突變情況March2012andApril2014N=130

突變陽性(46)突變陰性(17)DCR93%59%RR59%29%PFS13.1m5.6mNEnglJMed2015;372:1700-1709April30,2015DOI:10.1056/NEJMoa1413654BestResponsetoRociletinib:Eachbarrepresentsanindividualpatient,andtheamplitudeanddirectionofthebarrepresentthepercentchangeintumorburdenduringtreatmentascomparedwithbaseline.Tumorburdenwasmeasuredasthesumofthelongestdiametersofthetargetlesions,accordingtotheResponseEvaluationCriteriainSolidTumors,version1.1.Thedashedlineat20%representstheboundaryfordeterminationofprogressivedisease,andthedashedlineat?30%representstheboundaryfordeterminationofpartialresponse.FBdenotesfreebase,andHBrhydrogenbromidesalt.RociletinibinEGFR-MutatedNon–Small-CellLungCancer(NCT01526928)N=253TKIARNSCLCMarch6,2013~August1,2014T790突變情況N=253

突變陽性(138)突變陰性(62)RR61%（127）21%（61）PFS9.6m2.8mNEnglJMed.

2015Apr30;372(18):1689-99.doi:10.1056/NEJMoa1411817.AZD9291inEGFRInhibitor–ResistantNon–Small-CellLungCancer(NCT01802632)AZD9291AZD9291inEGFRInhibitor–ResistantNon–Small-CellLungCancer(NCT01802632)AZD9291inEGFRInhibitor–ResistantNon–Small-CellLungCancer(NCT01802632).AZD9291inEGFRInhibitor–ResistantNon–Small-CellLungCancer(NCT01802632)前景展望3代TKI藥物應用于耐藥的晚期NSCLC患者前景良