吉非替尼的循證之路賈筠東莞市人民醫(yī)院易瑞沙的歷史正是肺癌靶向治療的歷史的縮影Cohensdiscoveryofepidermalgrowthsolaronofhumanfactor(EGF)inmiceinhigrowth/differentiationinhibited1994research2000DiscoveryofFirstewclassofEAPstartsinparallelwithAstraZenecaPhaseltrialsDEALIINTACT)July:JapaneseapprovalApnl:EGFR-TKmutationsdannythemechansm2003August:INTACTstudiesMay:USDeerbersveralpulashownoaddedbenefitaddingIRESSAtostandardapprovaladvantageounsshowbenefit1stlinedoublet2008chemotherapyforNSCLC2007ASSResultsv-15-32/2ndline-NSCLCAVApprovalsin36countriesternatefirstdirectcomparisondocetaxel-JapanofEGFR-TKIvschemotherapyINTEREST(2ndlineNSCLCVSpublishednormingabouISELbiomarkeranalysissuggestscetaxeINSTEPinapaFISHtpatientsmorelikelytobenefit易瑞沙在中國●全球和中國第一個(gè)上市的EGFR-TK●啟動(dòng)了中國NSCLC的靶向研究●將中國醫(yī)生帶上了國際靶向研究的歷史舞臺(tái),由此開始中國肺癌靶向新紀(jì)元。●伴隨著研發(fā)的不斷深入,共識(shí)在爭(zhēng)論中顯現(xiàn)吉非替尼從二線到一線的跨越吉非替尼在中國爭(zhēng)議與共識(shí)吉非替尼從二線到一線的跨越吉非替尼在中國爭(zhēng)議與共識(shí)NSCLCMovingBeyondtheSnail'sPaceoFerryD,theUniversityofBirminghaminEngland■PR:4/16(25%)oKusabah,theNationalCancerCenterinJapanPR:5/23(21%)oGossGtheNationalCancerInstituteofCanada■藥代動(dòng)力學(xué):抑制EGFR-TK的自主磷酸化由此啟動(dòng)了臨床試驗(yàn):二線單藥(phase2)一線聯(lián)合化療(phase3)2000.AScOIDEAL1and2首次發(fā)現(xiàn)易瑞沙療效與種族相關(guān)總體日本亞組n=20970.4250m51.4500mg5027.518.419.0ORRDCRORRDCRMST(Month)7.6MST(Month)13.81-YearSurvival1-YearSurvival:57%PFS(MonthPFS(Month):3.8DEAL1Fukuokaetal2003FDAU.S.FoodandDrugAdministrationfaCENTERFORDRUGEVALUATIONANDRESEARCHDrugsFDAFAQInstructionsGlossaryContactUs|CDERHomeFDAApprovedDrugProductsStartOv。rDrugDetailsDrugName(s)IRESSA(BrandNameDrug)FDAApp|icat。nN。(NDA)021399ActiveIngredient(s)GEFITINIBCompanASTRAZENECAOriginalApprovalorTentativeApprovalDateReviewclassificationrityreviewdrugTherearenoTherapeuticEquivalentsLabelInformationApprovalHistory,Letters,ReviewsandOtherImportantInformationfromFDARelatedDocumentSEL:吉非替尼VS安慰劑所有人群總生存期延長(zhǎng)但未達(dá)顯著性差異吉非替尼安慰劑生存率中位生存期(月)5.65.11年生存率(%)0.8Log-rankHR(95%C),0.89(0.77,1.02);p=0.087;Coxanalysis,p=0.0300.60.40.0(月)HR,hazardratio;cl,confidenceintervalThatcherNetal.2005LabelChangeForCancerDrugIreeealnefitinihl美國FDA修改ressa的適應(yīng)癥18Jun2005int只能用于有效的晩期肺癌患者AstraZenecaannouncedthatafterdiscussionswiththeUSFoodandDrugAdministration(FDA),thecompanyismakingalabelingchangetoIRESSAD(gefitinibtablets).BasedontheFDAsassessmentIofcurrentlyavailabledata,includingthelackofsurvivalbenefitinthePhasellTrialcomparingIRESSAtoplaceboinadvancedrecurrentnon-small-celllungcancer(NSCLC),andtheavailabilityofothertreatmentoptionsintheUnitedStatesthatdoprolonglife,therevisedlabelindicatesthatIRESSAisonlytobeusedinpatientswhohavepreviouslytakenIRESSAandarebenefitingorhavebenefitedfromIRESSA.Inaddition,IRESSAwillcontinuetobeavailableforuseclinicaltrialsapprovedbyanInstitutionalReviewBoard(IRB)priortoJune17,2005.ClinicaltrialsapprovedbyanIRBafterJune17,2005,mustbeconductedunderaninvestigationalnewdrugapplication(IND).Toimplementthenewlabel,asofSeptember15,2005,AstraZenecawillinitiatetheIRESSAAccessProgramtofillrenewalprescriptionsforIRESSAthroughasinglemailorderpharmacyforpatientsmeetingthecriteriasetforthbythelabel.IRESSAwillremainavailableintheUnitedStates,throughtheIRESSAAccessProgram,forpatientswhoarecurrenthybenefitingorwhohavebenefited,