肺癌靶向治疗研究进展

晚期非小细胞肺癌EGFR-TKI获得性耐药的热点研究及进展主要内容：•EGFR-TKI作用机制、耐药机制•新药临床研究•前景展望kkkEGFRPPERBB3PPPPAKTKRASJak/StatPEGFR信号传导的分子机制JkkkEGFRPPPTKIGefitinibErlotinibKRASXJak/StatXAKTXEGFR-TKI作用机制主要内容：•EGFR-TKI作用机制、耐药机制•新药研究•前景展望EGFR-TKI耐药机制5%3%2%11%23%2%3%T790kkkEGFRPERBB3PPAKTKRASJak/StatPT790GefitinibErlotinibT790M介导EGFR-TKI耐药机制EGFR-TKI耐药热点研究梳理EGFR-tki耐药其他T790突变MET扩增3代TKI2代TKIMET抑制剂TivantinibonartuzmabAfatinibDacomitinibCO1686/AZD9291RR10%PFS小于4mC01686——RociletinibRociletinibinEGFR-MutatedNon–Small-CellLungCancer(NCT01526928)N=130TKIARNSCLCT790突变情况March2012andApril2014N=130突变阳性(46)突变阴性(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突变情况N=253突变阳性(138)突变阴性(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1.3代TKI药物应用于耐药的晚期NSCLC患者前景良好。2.Ⅰ~Ⅱ期临床试验已完成，期待Ⅲ期临床试验结果（目前患者仍在招募中）。预计2~3年T790耐药治疗将得到突破。3.肺癌耐药是一个多靶向、多方向的过程，还将有更长的路要走，期待大家共同完成。