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1、非小細胞肺癌靶向治療內(nèi)容分子靶向微環(huán)境腫瘤干細胞內(nèi)容分子靶向微環(huán)境腫瘤干細胞Nomutation,nopathway,nodrugs.分子標志物的發(fā)現(xiàn)帶來NSCLC分類改變LancetOncol.2011Feb;12(2):175-80.病理學(xué)分類分子分型更精確指導(dǎo)治療、判斷預(yù)后。NSCLC已知驅(qū)動基因及藥物轉(zhuǎn)化http://www.mycancergenome.org/content/disease/lung-cancer97%的突變彼此互相排斥。在所有突變中,EGFR、ALK獲得成功轉(zhuǎn)化。EGFRTKI(厄洛替尼、吉非替尼、阿法替尼)克唑
2、替尼Krisetal.JClinOncol29:2011(suppl;abstr7506)EGFRTKI應(yīng)用晚期NSCLC一線治療的2個重要議題EGFR突變患者一線先TKI或含鉑雙藥EGFRTKI耐藥后策略O(shè)PTIMAL:厄洛替尼VS.吉西他濱順鉑WJTOG3405:吉非替尼VS.多西他賽順鉑LUX-LUNG3:阿法替尼VS.培美曲塞順鉑OPTIMAL研究設(shè)計CaicunZhou,et,al,2012,ASCO,PosterDiscussionSession,7520#厄洛替尼150mg/天直至進展未經(jīng)化療IIIB/IV期NSCLCEGFR
3、基因突變(外顯子19或L858R)ECOGPS0–2N=165Gemcitabine(1,000mg/m2d1,8)+carboplatin(AUC5d1)q3w,upto4cyclesR1:1分層因子突變類型組織學(xué)吸煙狀態(tài)ActMut+=activating突變s;ECOG=EasternCooperativeOncology組;PS=performancestatusHRQoL=health-relatedqualityoflife;FACT-L=FunctionalAssessmentofCancerTherapy-Lung;LCS
4、S=lungcancersymptomscale主要終點:無進展生存(PFS)次要終點:總生存(OS),客觀有效率(ORR),疾病進展時間,有效持續(xù)時間,HRQoL(FACT-L,LCSS),生物標記分析療效評價每6周OPTIMAL:主要研究終點PFS結(jié)果PFSprobability1.00.80.60.40.20051015202530Time(months)PatientsatriskTarceva82705129820G/C722641000nEvents,n(%)Median,months95%CI8258(70.73)13.71
5、0.58–15.287264(88.89)4.64.21–5.42HR=0.164(95%CI:0.105–0.256)Log-rankp<0.0001TarcevaG/CZhou,etal.ASCO2012,abstr7520OPTIMAL:ITT總體人群的OS結(jié)果PatientsatriskErlotinib8281736450402030GC72686053453919301.00.80.60.40.200510152025303540Time(months)OSprobabilitynEventsn(%)Median(months)
6、95%CIErlotinib8250(61)22.6920.07–30.39GC7242(58)28.8522.87–31.47Log-rankp=0.6915HR(95%CI):1.04(0.69–1.58)Zhou,etal.ASCO2012,abstr7520OPTIMAL:ITT人群兩個治療組的后續(xù)治療后續(xù)治療,n(%)Erlotinib,n=82GC,n=72無疾病進展(仍在接受研究藥物的治療)7(9)0無研究后續(xù)治療25(30)16(22)二線治療EGFRTKI化療其他?50(61)1(1)43(52)*6(7)56(78)46(
7、64)9(13)1(1)后續(xù)EGFRTKI治療§8(10)51(71)Note:apatientmayappearinmorethanonepost-studytreatmentgroup*Themediannumberof2nd-linechemotherapycyclesintheerlotinibarmwastwo?Patientsparticipateinotherclinicaltrials§PatientsreceivetreatmentinanylineZhou,etal.ASCO2012,abstr7520OPTIMAL:預(yù)先
8、設(shè)定的交叉治療組的OS分析結(jié)果PatientsatriskErlotinibarmreceiving2nd-linechemo50484236321730GCarm