吉非替尼的循证之路

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1、吉非替尼的循证之路贾筠东莞市人民医院1980sMendelsohnproposesEGFRasanticancertarget1983Firstanti-EGFRagents(mAbs)1990sFirstclinicaltrialofanti-EGFRagent(mAb)confirmsMOA1994DiscoveryofnewclassofEGFR-TKIsbyAstraZeneca1997FirstclinicaltrialsconfirmMOAofIRESSA.1998Favourabletolerabilityandunprecedented

2、responsesinPhaseItrials,reportedatNCI-EORTC-AACR,HKellyetal2000EAPstartsinparallelwithPhaseII/IIItrials(IDEAL/INTACT)2002July:JapaneseapprovalAugust:INTACTstudiesshownoaddedbenefitofaddingIRESSAtostandard1stlinedoubletchemotherapyforNSCLC2003May:USapproval2004April:EGFR-TKmutati

3、onsclarifythemechanismforsomeofthedramaticresponsesproducedDecember:ISELdatademonstratenosurvivaladvantageoverBSCinoverallpopulation,thoughsubgroupsshowbenefit2005Approvalsin36countriestodateSIGNdata–firstdirectcomparisonofEGFR-TKIvschemotherapyISELbiomarkeranalysissuggestsFISH+

4、patientsmorelikelytobenefitfromIRESSA2006INVITE(1stlineNSCLC)IMEX(H&Ncancer)September:CCSdatapublishedinformingaboutILDinJapan2007V-15-32(2ndlineNSCLCvsdocetaxel—Japan)INTEREST(2ndlineNSCLCvsdocetaxel)INSTEP1977IdentificationofEGFreceptorbyCohen1975IsolationofhumanEGF/urogastron

5、efromhumanurinebyCohen(VanderbiltUniv.)andGregory(ICI)1984HumanEGFRclonedandsequencedLate1980sAccumulatingevidencethatEGFRisassociatedwithtumourprogressionandthatEGFRkinaseactivitycanbeinhibitedinvitrobysmallmolecules1960sCohen’sdiscoveryofepidermalgrowthfactor(EGF)inmicein1962p

6、ioneersmajorprogressincellgrowth/differentiationresearch.2008IPASSResults易瑞沙的历史正是肺癌靶向治疗的历史的缩影易瑞沙在中国全球和中国第一个上市的EGFR-TKI启动了中国NSCLC的靶向研究将中国医生带上了国际靶向研究的历史舞台，由此开始中国肺癌靶向新纪元。伴随着研发的不断深入，共识在争论中显现吉非替尼从二线到一线的跨越吉非替尼在中国争议与共识吉非替尼从二线到一线的跨越吉非替尼在中国争议与共识FerryD,theUniversityofBirminghaminEnglandPR

7、：4/16（25%）KusabaH,theNationalCancerCenterinJapanPR：5/23（21%）GossG,theNationalCancerInstituteofCanada药代动力学:抑制EGFR-TKI的自主磷酸化NSCLCMovingBeyondtheSnail'sPace2000，ASCO由此启动了临床试验：二线单药（phase2)一线联合化疗（phase3)总体n=209日本亚组n=102Patients(%)ORRDCR54.451.418.419.0010203040506070ORRDCR70.470.627.

8、527.5010203040506070250mg500mgIDEAL1and2首次发现易瑞沙