維持治療修改版

對(duì)一線維持治療的思考中國醫(yī)學(xué)科學(xué)院腫瘤醫(yī)院非小細(xì)胞肺癌流行病學(xué)回顧近半個(gè)世紀(jì)以來，特別是吸煙的流行，接近20世紀(jì)中葉時(shí)，肺癌的發(fā)病率和死亡率先是在發(fā)達(dá)國家、隨后在發(fā)展中國家迅速增高。1985年起肺癌已成為全世界最常見的惡性腫瘤。2002年全世界肺癌新發(fā)病例約135萬、死亡病例約118萬。肺癌是全球范圍內(nèi)導(dǎo)致癌癥死亡的第一位病因１。而非小細(xì)胞肺癌（NSCLC）占新診斷肺癌的80%以上2。2006年，我國城鎮(zhèn)人口中惡性腫瘤發(fā)病率已經(jīng)超越心腦血管疾病，并成為首要死因。而肺癌又在惡性腫瘤中居首，已成為中國的第一大癌。1、ParkinMD,etal.CACancerJClin2005;55:74-108.2、GovindanR,etal.JClinOncal2006;24:4539-4544.不同病理類型的發(fā)病率：中國上海為例鄭瑩等,診斷學(xué)倫理與實(shí)踐

2006;5(2):126-130.N=10184男性女性腺癌鱗癌小細(xì)胞癌既往NSCLC治療的模式由于蓄積毒性，患者只能接受有限的化療周期ASCO指南推薦，對(duì)療效為SD或更好的患者應(yīng)進(jìn)行定期隨訪直到疾病進(jìn)展，即采用“觀察并等待”的策略1確診CR/PR/SD一線治療含鉑兩藥化療

(4–6周期)‘觀察并等待’PD二線或后續(xù)治療PD1PfisterDG,etal.JClinOncol2004;22:330–53一線化療進(jìn)展后也許無法接受后續(xù)治療Inrecentstudies,approximately50%ofpatientsdidnotreceivesecond-linetherapy0255075100Fidiasetal.2009Scagliottietal.2008Pirkeretal.2008Ciuleanuetal.2008Parketal.2007Barataetal.2007vonPlessenetal.2006Brodowiczetal.2006Belanietal.2003Socinskietal.2002Patientsreceiving2nd-linetherapy(%)確診CR/PR/SD一線治療含鉑兩藥化療

(4–6周期)‘觀察并等待’PD二線或后續(xù)治療PD維持治療（maintenancetherapy）死亡維持治療——晚期NSCLC治療新模式一線化療未PD的患者繼續(xù)接受治療的目的：延緩疾病進(jìn)展延緩癥狀惡化延緩死亡時(shí)間增加后續(xù)治療（化療）機(jī)會(huì)診斷PD二線治療直到PD死亡一線治療

含鉑兩藥化療(4–6周期)CR/PR/SD維持治療新模式維持治療研究背景一:

以鉑類為基礎(chǔ)的兩藥聯(lián)合化療療效瓶頸ResponseRate*MST:7.4-10.3Months1YS:26%-43%DatafromprospectiverandomizedphaseIIItrialswith~4000patientsparticipated嘗試一：三藥不優(yōu)于兩藥！DelbaldoC.etal.,JAMA2004;292:470三藥化療緩解率雖好于兩藥，但未轉(zhuǎn)化為更多的生存獲益，且毒性無法耐受嘗試二：繼續(xù)一線兩藥化療直到4-6個(gè)周期中位周期數(shù)(范圍)MST，月(范圍)Socinskietal,ArmA(standard)4(0–6)6.6(5.4–9.0)Socinskietal,ArmB(extended)4(0–19)8.5(6.3–10.3)Parketal,ArmA(2+4cycles)6(2–6)14.9(13.0–16.8)Parketal,ArmB(2+2cycles)4(2–4)15.9(12.4–19.4)SocinskiMA,etal.JClinOncol2002;20:1335–1343.

ParkJO,etal.JClinOncol2007;25:5233–5239.3-4周期后延長化療將導(dǎo)致毒性累積，但沒有確切的療效(生存)優(yōu)勢(shì)嘗試三：

一線兩藥化療藥物中某一化療藥物維持治療T.E.Stinchcombe,andMarkA.Socinski,JTO2009顯著延長PFS但OS的延長沒有統(tǒng)計(jì)學(xué)意義增加了不良反應(yīng)并影響了生活質(zhì)量嘗試四：二線治療的化療藥物提前應(yīng)用多西他賽顯著延長PFS但OS的延長沒有統(tǒng)計(jì)學(xué)意義，明顯增加了不良反應(yīng)并影響了生活質(zhì)量T.E.Stinchcombe,andMarkA.Socinski,JTO2009立即多西他賽與延遲多西他賽的研究設(shè)計(jì)Fidias,etal.JCO2009卡鉑吉西他濱

(4周期)立即多西他賽BSCCR,PRSD延遲多西他賽PD隨機(jī)分組主要終點(diǎn)：總生存期入組標(biāo)準(zhǔn)：IIIB/IV期NSCLC，既往未化療，ECOGPS0–2立即多西他賽與延遲多西他賽：PFSHR=0.71(0.55–0.92)Log-rankp=0.00011.00.20無進(jìn)展生存概率

0 6 12 18 24 30 36 42 48時(shí)間(月)立即組(n=153) 延遲組(n=156)Fidias,etal.JCO2009立即多西他賽與延遲多西他賽：OSFidias,etal.JCO20091.00.20

0 6 12 18 2430 3642 485460時(shí)間(月)生存概率立即組(n=153) 延遲組(n=156)HR=0.84(0.65–1.08)Log-rankp=0.085C.P.Belani1,T.Brodowicz2,3,T.Ciuleanu3,4,J.H.Kim5,M.Krzakowski3,6*,E.Laack7,Y.L.Wu8,P.Peterson9,K.Krejcy10,C.Zielinski2,1PennStateHersheyCancerInstitute,Hershey,PA,USA;2MedicalUniversity,Vienna,Austria;3CentralEuropeanCooperativeOncologyGroup(CECOG);4InstitutulOncologicIChiricuta,Cluj,Romania;5YonseiCancerCenter,Seoul,Korea;6MariaSklodowska-CurieMemorialCancerCenter&InstituteOfOncology,Warsaw,Poland;7CancerCenter,UniversityHospitalHamburg-Eppendorf,Germany;8GuangdongGeneralHospital,Guangzhou,China;9EliLillyandCo.IN,USA;10LillyRegionalOperations,Vienna,Austria雙盲，多中心，安慰劑對(duì)照的Pemetrexed維持治療NSCLCIII期臨床研究

JMENStudyStageIIIB/IVNSCLCECOGPS0-14priorcyclesofgem,doc,ortax+cisorcarb,withCR,PR,orSDRandomizationfactors:genderPSstagebesttumorresponsenon-platinumdrugbrainmets*B12,folate,anddexamethasonegiveninbotharmsDouble-blind,Placebo-controlled,Multicenter,PhaseIIITrialJMEN：研究設(shè)計(jì)

PrimaryEndpoint=PFS2:1RandomizationPemetrexed500mg/m2(d1,q21d)+BSC(N=441)*Placebo(d1,q21d)+BSC(N=222)*JMEN：PFSandOSProbabilityTime(months)Progression-freesurvival

(n=581)Overallsurvival

(n=663)1.00.20

0 3 6 9 12 15 18 21 24 0 6 12 18 24 30 36 42 48Time(months)1.00.20HR=0.599(95%CI:0.49–0.73)p<0.00001Pemetrexed:4.0monthsPlacebo:2.0monthsPemetrexed:13.4monthsPlacebo:10.6monthsHR=0.79(95%CI:0.65–0.95)p=0.012Belani,etal.ASCO2009鱗癌患者無法從培美曲塞治療中獲益總生存期培美曲塞安慰劑PHR非鱗癌(n=482)15.510.30.0020.70腺癌(n=329)16.811.50.0260.73大細(xì)胞癌(n=20)640.98其他(n=133)250.61鱗癌(n=181)9.910.80.6781.07Interactionptest，p=0.033BelaniCPetal,ASCO2009;AbstractCRA:8000.JMEN：鱗癌和東亞裔亞組顯示培美曲塞維持治療不獲益CappuzzoFetal,ASCO2009;AbstractNo:8001.BelaniCPetal,ASCO2009;AbstractCRA:8000.安慰劑有利0.00.81.01.8培美曲塞有利腺癌(n=328)鱗癌(n=182)高加索裔(n=428)東亞裔(n=154)其他種族(n=81)總生存JMEN:后續(xù)治療選擇Pemetrexed

n=441(%)Placebo

n=222(%)AnysystemictherapyDocetaxelErlotinibGefitinib5222221367292110Pemetrexed119Belani,etal.ASCO2009JMEN研究局限患者選擇局限：

鱗癌和東亞患者不獲益后續(xù)治療局限：后續(xù)治療特別是化療機(jī)會(huì)低于安慰劑組生活質(zhì)量局限：和安慰劑比較Qol無改善。2009ASCOEducationSession

5大避免化療作為維持治療的原因靜脈使用不方便(Veinsbecomeinaccessible)患者不愿意(Patientsbecomeinaccessible)長期化療的蓄積毒性(尤其含鉑方案)(Cumulativetoxicityoflong-termtherapy,especiallyplatinum-based)對(duì)于患者和護(hù)理人員，維持化療耗費(fèi)時(shí)間，并且不方便[Timeandinconvenienceforpatientsandcaregiver]最關(guān)鍵的是，你希望讓你的患者接受長期的化療嗎？[Wouldyouwantlongdurationchemotherapy?]維持治療研究背景二:

以鉑類為基礎(chǔ)的兩藥聯(lián)合化療+TKITrialChemoRegimenRR

(%)TTP

(months)OS(months)INTACT1GEM/CISGEM/CIS/G250GEM/CIS/G50065.85.5INTACT2CAR/PACCAR/PAC/G250CAR/PAC/G50028.730.4309.88.7TALENTGEM/CISGEM/CIS/E15028.2305.65.410.19.9TRIBUTECAR/PACCAR/PAC/E15019.310.610.8GandaraDRetal,ClinicalLungCancer2006,7(6):385-388.TALENT研究：特羅凱維持治療顯示獲益Gatzemeier,Uetal.JClinOncol2007;25:1545–1552.0 10 20 30 40 50 60(周)1.00.20生存概率(%)化療階段Log-rankp=0.0453特羅凱+化療安慰劑+化療隨機(jī)，雙盲，安慰劑對(duì)照的

特羅凱維持治療一線含鉑兩藥化療后無進(jìn)展的晚期NSCLC病人III期臨床研究FedericoCappuzzo1,

TudorCiuleanu2,

LiliaStelmah3,SauliusCicenas4,

AleksandraSzczesna5,ErzsebetJuhasz6,EmilioEstebanGonzalez7,

OlivierMolinier8,GaelleKlingelschmitt9,GiuseppeGiaccone10,onbehalfoftheSATURNinvestigators

1IstitutoClinicoHumanitasIRCCS,Rozzano(Milan),Italy;2InstituteofOncologyIonChiricuta,Cluj-Napoca,Romania;3PavlovStateMedicalUniversity,StPetersburg,RussianFederation;4InstituteofOncology,VilniusUniversity,Vilnius,Lithuania;5MazowieckieCentrumLeczeniaChorobPlucIGruzlic,Otwock,Poland;6KoranyiNationalInstituteforPulmonology,Budapest,Hungary;7HospitalUniversitarioCentraldeAsturias,Oviedo,Spain;8CentreHospitalierLeMans,LeMans,France;9F.Hoffmann-LaRocheLtd,Basel,Switzerland;10CCR,NationalCancerInstitute,NIH,Bethesda,MDF.Cappuzzo.etal,JClinOncol27:7s,2009(suppl;abstr8001)SATURN研究SATURN研究設(shè)計(jì)TITANoroffstudy(n=889)既往未化療的IIIB/IVNSCLCn=1,949CR,PR,SD1:14周期一線含鉑兩藥標(biāo)準(zhǔn)化療*PD安慰劑PDOffstudy特羅凱150mg/dPDOffstudy腫瘤樣本(強(qiáng)制性)根據(jù)EGFR免疫組化蛋白表達(dá)分層F.Cappuzzo.etal,JClinOncol27:7s,2009(suppl;abstr8001)*含鉑方案可以為以下任何之一：紫杉醇，吉西他賓，多西他賽+順鉑或卡鉑；長春瑞賓+順鉑主要終點(diǎn):

PFSinallpatients

PFSinEGFRIHC+基線條件特羅凱(n=438)安慰劑(n=451)中位年齡60.0(33–83)59.0(30–81)男/女,%73/2775/25IIIB/IV期,%26/7424/76高加索裔/亞裔/其他,%84/14/283/15/2ECOGPS0/1,%31/6932/68現(xiàn)/曾/從不吸煙,%55/28/1856/27/17腺癌+BAC/鱗癌/其他,%47/38/1544/43/13對(duì)之前化療的反應(yīng),CR/PR/SD<1/42/58<1/47/52是否手術(shù),是/否,%58/4254/46是否放療,是/否,%11/8910/90SATURN研究：基線條件F.Cappuzzo.etal,JClinOncol27:7s,2009(suppl;abstr8001)主要終點(diǎn)PFS*:ITT患者PFSprobability1.00.20 0 8 16 24 32 40 48 56 64 72 80 88 96Time(weeks)HR=0.71(0.62–0.82)Log-rankp<0.0001Erlotinib(n=437)Placebo(n=447)ErlotinibPlaceboPFSat12wks(%)5340PFSat24wks(%)3117*PFS從隨機(jī)化開始接受維持治療計(jì)算；每6周評(píng)估一次F.Cappuzzo.etal,JClinOncol27:7s,2009(suppl;abstr8001)PFSandOS兩個(gè)主要終點(diǎn)：ITT人群 0369121518212427303336Time(months)OSprobability1.00.20Tarceva(n=438)Placebo(n=451)11.012.0*OSismeasuredfromtimeofrandomisationinto

themaintenancephase

HR=0.81(0.70–.95)Log-rankp=0.0088Cappuzzo,etal.WCLC20091.00.20Time(weeks)HR=0.71(0.62–0.82)Log-rankp<0.0001Tarceva(n=437)Placebo(n=447)PFSat12weeks(%)5340PFSat24weeks(%)3117*PFSismeasuredfromtimeofrandomisationintothemaintenancephase;assessmentswereevery6weeks;ITT=intent-to-treatpopulationPFSprobabilityCappuzzo,etal.WCLC200941%improvementinPFS23%improvementinOS 081624324048566472808896一線化療不同療效的PFSPFSprobability1.00.20 0 8 16 24 32 40 48 56 64 72 80 88 96Time(weeks)Log-rankp<0.0001HR=0.68(0.56–0.83)Erlotinib(n=252)Placebo(n=235)11.112.4SDLog-rankp=0.0059HR=0.74(0.60–0.92)Erlotinib(n=184)Placebo(n=210)11.312.1CR/PR1.00.20 0 8 16 24 32 40 48 56 64 72 80 88 96Time(weeks)聯(lián)合主要終點(diǎn)PFS*:IHC+患者1.00.20 0 8 16 24 32 40 48 56 64 72 80 88 96Time(weeks)HR=0.69(0.58–0.82)Log-rankp<0.0001Erlotinib(n=307)Placebo(n=311)ErlotinibPlaceboPFSat12wks(%)5440PFSat24wks(%)3218*PFS從隨機(jī)化開始接受維持治療計(jì)算；每6周評(píng)估一次F.Cappuzzo.etal,JClinOncol27:7s,2009(suppl;abstr8001)PFSprobability各亞組PFS獲益分析所有人群男性女性高加索裔亞裔腺癌

鱗癌從不吸煙曾吸煙目前吸煙 HR(95%CI) n 0.71(0.62–0.82) 884 0.78(0.66–0.92) 654 0.56(0.42–0.76) 230 0.75(0.64–0.88) 744 0.58(0.38–0.87) 128 0.60(0.48–0.75) 401 0.76(0.60–0.95) 359 0.56(0.38–0.81) 152 0.66(0.50–0.88) 242 0.80(0.67–0.97) 4901.01.2Favours

TarcevaFavours

placeboHRF.Cappuzzo.etal,JClinOncol27:7s,2009(suppl;abstr8001)生物標(biāo)志物和PFS關(guān)聯(lián)分析所有人群EGFRIHC+EGFRIHC–EGFRFISH+EGFRFISH–KRASmutation+KRASwild-typeKRASunknownn88461812123125590403390HR(95%CI)0.71(0.62–0.82)0.69(0.58–0.82)0.77(0.51–1.14)0.68(0.51–0.90)0.81(0.62–1.07)0.77(0.50–1.19)0.70(0.57–0.87)0.70(0.56–0.87)Favours

placebo1.01.2Favours

TarcevaHRF.Cappuzzo.etal,JClinOncol27:7s,2009(suppl;abstr8001)疾病控制≥12周*患者(%)50250

特羅凱 安慰劑

(n=436) (n=445)*CR+PR+SD≥12周p<0.000140.8%27.4%F.Cappuzzo.etal,JClinOncol27:7s,2009(suppl;abstr8001)13.4%OS*:ITT患者

0 3 6 9 12 15 18 21 24 27 30 33 36Time(months)OSprobability1.00.20Erlotinib(n=438)Placebo(n=451)11.012.0*OSismeasuredfromtimeofrandomisationintothemaintenancephase;

ITT=intent-to-treatpopulationHR=0.81(0.70–0.95)Log-rankp=0.0088F.Cappuzzo.etal,WCLC,Abs#No:A2.1

OS*:一線化療后SD的患者OSprobability1.00.20 0 3 6 9 12 15 18 21 24 27 30 33 36Time(months)9.611.9*OSismeasuredfromtimeofrandomisationintothemaintenancephaseErlotinib(n=252)Placebo(n=235)HR=0.72(0.59–0.89)Log-rankp=0.0019OS*：一線化療后不同療效的OSOSprobability1.00.20 0 3 6 9 12 15 18 21 24 27 30 33 36Time(months)9.611.91.00.20 0 3 6 9 12 15 18 21 24 27 30 33 36Time(months)12.012.5Log-rankp=0.0019HR=0.72(0.59–0.89)Erlotinib(n=252)Placebo(n=235)Log-rankp=0.6181HR=0.94(0.74–1.20)Erlotinib(n=184)Placebo(n=210)SDCR/PR*OSismeasuredfromtimeofrandomisationintothemaintenancephase一線化療后不同療效的OS：安慰劑組

OSOSprobability1.00.20 0 3 6 9 12 15 18 21 24 27 30 33 36Time(months)9.612.0*OSismeasuredfromtimeofrandomisationintothemaintenancephaseSDon1st-linechemotherapy(n=235)CR/PRon1st-linechemotherapy(n=210)

一線化療后不同療效的OS：厄洛替尼組

OSOSprobability1.00.20 0 3 6 9 12 15 18 21 24 27 30 33 36Time(months)11.912.5*OSismeasuredfromtimeofrandomisationintothemaintenancephaseSDonfirst-linechemotherapy(n=252)CR/PRonfirst-linechemotherapy(n=184)一線化療后不同療效的OS：安慰劑組

OSOSprobability1.00.20 0 3 6 9 12 15 18 21 24 27 30 33 36Time(months)9.612.0*OSismeasuredfromtimeofrandomisationintothemaintenancephaseSDon1st-linechemotherapy(n=235)CR/PRon1st-linechemotherapy(n=210)CR/PRon1st-linechemotherapyStudyarmSDon1st-linechemotherapyStudyarmControlarmControlarmSATURN：特羅凱維持治療顯著延長EGFR野生型患者的OS*EGFR突變型亞組67%的安慰劑組患者后續(xù)接受二線EGFR-TKI治療

0 3 6 9 12 15 18 21 24 27 30 33 36OSprobability1.00.20Time(months)

0 3 6 9 12 15 18 21 24 27 30 33 361.00.20Time(months)EGFR野生型EGFR突變型Log-rankp=0.0243HR=0.77(0.61–0.97)Log-rankp=0.6810HR=0.83(0.34–2.02)特羅凱(n=199)安慰劑(n=189)特羅凱(n=22)安慰劑(n=27)NR23.8中位(月)BruggerWetal,WCLC2009.23%EGFR突變患者特羅凱維持治療中位總生存未達(dá)到統(tǒng)計(jì)學(xué)差異，這和安慰劑組后續(xù)治療中用了很高比例的TKI藥物有關(guān)——WolframBruggeronWCLC生物標(biāo)志物和OS關(guān)聯(lián)分析All

EGFRIHC+EGFRIHC-*EGFRmutation+EGFRwild-type1.01.2Favours

erlotinibFavours

placeboHR2.0

HR(95%CI) n 0.81(0.70–0.95) 889

0.77(0.64–0.93) 621 0.91(0.59–1.38) 121

0.83(0.34–2.02) 49 0.77(0.61–0.97) 388*67%ofpatientswithEGFRmutation+diseaseintheplaceboarmreceivedasecond-lineEGFRTKIF.Cappuzzo.etal,WCLC,Abs#No:A2.1，

生活質(zhì)量分析–

顯著延長疼痛惡化時(shí)間HR(95%CI)p至生活質(zhì)量惡化時(shí)間(FACT-L)0.96(0.79–1.16)0.6530疼痛0.61(0.42–0.88)0.0080咳嗽0.77(0.49–1.21)0.2546呼吸困難0.75(0.48–1.17)0.2054服用止痛劑0.66(0.46–0.94)0.0199FACT-L=FunctionalAssessmentofCancerTherapy–Lungquestionnaire;

QoL=qualityoflifeF.Cappuzzo.etal,WCLC,Abs#No:A2.1，

Erlotinib

(n=438)Placebo

(n=451)%withatleastonetreatmentAllclasses7172taxanes(includingdocetaxel)3031antimetabolites(includingpemetrexed)2423antineoplasticagents1618tyrosine-kinaseinhibitors1121platinumcompounds912后續(xù)治療選擇F.Cappuzzo.etal,WCLC,Abs#No:A2.1

SATURN：結(jié)論特羅凱能夠顯著增加IIT人群PFS及OS;在EGFR突變以外的患者顯示出了生存益處；特羅凱維持治療比較安慰劑組：所有患者群都顯示臨床獲益，無論組織學(xué)類型，種族或吸煙狀態(tài)達(dá)到了主要終點(diǎn)和聯(lián)合主要終點(diǎn)，降低了29%疾病進(jìn)展風(fēng)險(xiǎn)（P<0.0001)提高腫瘤緩解率和疾病控制率(12%vs.5%；60.6%vs50.8%)，疾病控制持續(xù)12周以上的患者明顯增加（40.8%vs27.4%）提高了總生存，降低了19%的死亡風(fēng)險(xiǎn)（P=0.0088）生活質(zhì)量得到提高，延緩疼痛惡化時(shí)間增加了后續(xù)化療的機(jī)會(huì)重要的是：只有一線化療后達(dá)到SD的病人可以從特羅凱維持治療中獲得生存益處，提示這部分病人可能獲益最多。隨機(jī)，雙盲，安慰劑對(duì)照的

貝伐單抗聯(lián)合或不聯(lián)合厄洛替尼

維持治療局部進(jìn)展或轉(zhuǎn)移的NSCLC病人

III期臨床研究VincentA.Miller,MD,1PaulaO’Connor,MD,2Chang-HeokSoh,PhD,2andFairoozKabbinavar,MD,3fortheATLASInvestigators

1MemorialSloan-KetteringCancerCenter,NewYork,NY,2Genentech,Inc,SouthSanFrancisco,CA,3UniversityofCaliforniaLosAngeles–TranslationalOncologyResearchInternational,LosAngeles,CA

V.A.Miller.etal,JClinOncol27:7s,2009(suppl;abstrLBA8002)ATLAS研究

0 6 12 18 24 30 36 42 481.00.20月預(yù)期生存E4599:以貝伐單抗為基礎(chǔ)的治療可延長OSSandler,etal.NEJM200612.3<0.0030.79

(0.67–0.92)貝伐單抗

15mg/kg+CPCPHR

(95%CI)pvalue中位OS(月)10.3中位隨訪:19個(gè)月研究設(shè)計(jì)入組起止時(shí)間:2005年5月-2008年5月主要終點(diǎn):PFS次要終點(diǎn):安全性評(píng)估，OS*卡鉑/紫杉醇，卡鉑/多西他賽，順鉑/吉西他賓V.A.Miller.etal,JClinOncol27:7s,2009(suppl;abstrLBA8002)貝伐單抗15mg/kg+

特羅凱150mg/日貝伐單抗15mg/kg+

安慰劑既往未化療的IIIB/IV非鱗癌(n=1160)特羅凱150mg/日Non-PDOffstudyPDOffstudy(n=768)PD1:1貝伐單抗15mg/kg+化療*PD或不可耐受毒性入組患者分布情況NorthAmerica659Latin

America3AfricaEurope

27Asia

76Australia

3V.A.Miller.etal,JClinOncol27:7s,2009(suppl;abstrLBA8002)貝伐單抗+安慰劑

(n=373)*貝伐單抗

+特羅凱

(n=370)*中位年齡,歲(range)64(23-83)64(31-88)性別,%

男性

女性52.347.752.247.8種族,%

高加索裔

亞裔

其他77.712.110.2

疾病分期,%

IIIB

IV

復(fù)發(fā)10.285.65.7基線條件(ITT)V.A.Miller.etal,JClinOncol27:7s,2009(suppl;abstrLBA8002)基線條件(ITT)貝伐單抗+安慰劑

(n=373)*貝伐單抗

+特羅凱

(n=370)*ECOGPS,%0146.153.648.151.9吸煙狀態(tài),%

正在吸煙

曾吸煙

從不吸煙34.647.717.734.948.616.5病理學(xué)類型,%

腺癌

鱗癌

其他82.51.615.981.33.015.7是否曾經(jīng)接受放療,是,%15.317.3V.A.Miller.etal,JClinOncol27:7s,2009(suppl;abstrLBA8002)373142582715630370178814320631No.ofpatientsatrisk:Bev+PlaceboBev+Erlotinib無進(jìn)展生存(ITT)0369121518210.