晚期肠癌靶向治疗进展-徐瑞华教授

中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer Center晚期晚期肠癌靶向治癌靶向治疗进展展徐瑞徐瑞华 MD&PhD中山大学中山大学肿瘤医院内科瘤医院内科中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer Center主要内容主要内容以分子指以分子指标为指指导的靶向治的靶向治疗时代的来代的来临多个靶向多个靶向药物物联合的重新定位合的重新定位靶向靶向药物治物治疗的广泛研究的广泛研究中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterERBITUX in first-line treatment of mCRC中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterPhase III CRYSTAL study:Study designStratification factors:RegionECOG performance statusPopulations:Randomized patients(n=1217)Safety population(n=1202)ITT population(n=1198)FOLFIRIIrinotecan(180 mg/m2)+5-FU(400 mg/m2 bolus+2400 mg/m2 as 46-h continuous infusion)+LV(every 2 weeks)ERBITUX+FOLFIRIERBITUX(IV 400 mg/m2 on day 1,then 250 mg/m2 weekly)+irinotecan(180 mg/m2)+5-FU(400 mg/m2 bolus+2400 mg/m2 as 46-h continuous infusion)+LV(every 2 weeks)REGFR-expressing mCRC Van Cutsem E,et al.ASCO 2007(Abstract No.4000)中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer Center1.00.80.90.00.10.20.30.40.50.60.702468101214161820Primary endpoint:PFS(ITT population)PFS estimate Van Cutsem E,et al.ASCO 2007(Abstract No.4000)PFS time(months)1-year PFS rate:23%vs 34%FOLFIRI(n=599)ERBITUX+FOLFIRI(n=599)PFS ITT:HR=0.85;p=0.048mPFS ERBITUX+FOLFIRI:8.9 monthsmPFS FOLFIRI:8.0 months中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterIndependent assessment of response OutcomeFOLFIRI(n=599)(%)ERBITUX+FOLFIRI(n=599)(%)CRPRSDPD0.338.446.7 9.0 0.546.437.4 8.8ORR95%CI38.734.842.846.942.951.0DCR 85.4 84.3 Van Cutsem E,et al.ECCO 2007(Abstract No.3001)39%47%Response rate(%)p=0.0038aaCochranMantelHaenszel test中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterKRAS analysis:Objective and methodologyTo retrospectively investigate the impact of the KRAS mutation status of tumors on PFS and RR in the first-line treatment of mCRC with FOLFIRI ERBITUXEfficacy analyses repeated on KRAS evaluable populationGenomic DNA isolated from archived tumor materialParaffin-embedded,formalin-fixed tissueKRAS mutation status of codons 12/13 determined using quantitative PCR-based assay Van Cutsem E,et al.J Clin Oncol 2021;26(Suppl.abstract 2)中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterKRAS evaluable population587 subjects analysed for KRAS mutation status540(45%)subjects:KRAS evaluable population348(64.4%)KRAS wild-type192(35.6%)KRAS mutant171 subjects with events(49.1%)Group A:105(54.7%)Group B:87(45.3%)101 subjects with events(52.6%)1198 subjects(ITT)Group A:172(49.4%)Group B:176(50.6%)FOLFIRIERBITUX+FOLFIRI Van Cutsem E,et al.J Clin Oncol 2021;26(Suppl.abstract 2)中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterRelating KRAS status to efficacyPrimary endpoint:PFS KRAS wild-type0.00.10.20.30.40.50.60.70.80.91.0024681012141618MonthsProgression-free survival estimateERBITUX+FOLFIRIFOLFIRIKRAS wild-type(n=348)HR=0.68;p=0.017 mPFS ERBITUX+FOLFIRI:9.9 months mPFS FOLFIRI:8.7 months1-year PFS rate25%vs 43%Van Cutsem E,et al.J Clin Oncol 2021;26(Suppl.abstract 2)中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterRelating KRAS status to efficacyPrimary endpoint:PFS KRAS mutantKRAS mutant (n=192)HR=1.07;p=0.75mPFS ERBITUX+FOLFIRI:7.6 months mPFS FOLFIRI:8.1 months0246810121416MonthsERBITUX+FOLFIRIFOLFIRI0.00.10.20.30.40.50.60.70.80.91.0Progression-free survival estimate Van Cutsem E,et al.J Clin Oncol 2021;26(Suppl.abstract 2)中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterRelating KRAS status to efficacy:PFSERBITUX+FOLFIRI HR=0.63(p=0.007)Median PFS:Wild-type(n=172)9.9 months vs mutant(n=105)7.6 monthsFOLFIRI HR=0.97(p=0.87)Median PFS:Wild-type(n=176)8.7 monthsvs mutant(n=87)8.1 months0.51.00.40.30.20.10.00.60.70.80.9802461016PFS estimateTime(months)ERBITUX+FOLFIRI wild-typeERBITUX+FOLFIRI mutant12140.51.00.40.30.20.10.00.60.70.80.9Time(months)FOLFIRI wild-typeFOLFIRI mutant8024610161214PFS estimate Van Cutsem E,et al.J Clin Oncol 2021;26(Suppl.abstract 2)中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterRelating KRAS status to efficacySecondary endpoint:Responsep=0.0025aFOLFIRIERBITUX+FOLFIRIaCochran-Mantel-Haenszel(CMH)testKRAS wild-type(n=348)KRAS mutant(n=192)p=0.46aFOLFIRIERBITUX+FOLFIRI Van Cutsem E,et al.J Clin Oncol 2021;26(Suppl.abstract 2)中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterRelating KRAS status to outcome:Most common grade 3/4 adverse eventsKRAS wild-typeKRAS mutantAdverse events,%FOLFIRI(n=176)ERBITUX+FOLFIRI(n=173)FOLFIRI(n=87)ERBITUX+FOLFIRI(n=105)Any Neutropenia50.616.578.025.455.223.072.421.9 Febrile neutropenia Diarrhea0.69.10.617.3012.63.813.3Vomiting2.84.66.92.9Fatigue4.52.32.39.5Acne-like rasha016.2017.1Infusion-related reactions01.703.8aThere was no grade 4 acne-like rash Van Cutsem E,et al.J Clin Oncol 2021;26(Suppl.abstract 2)中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterConclusions:CRYSTAL studyAdding ERBITUX to FOLFIRI in mCRC leads to a significant increase in PFS(HR=0.85;p=0.048)The benefit of ERBITUX+FOLFIRI is greater in patients with KRAS wild-type tumors:PFS(HR=0.68;p=0.017)Response rate 59%vs 43%(p=0.0025)The grade 3/4 adverse-event profile was similar in the KRAS wild-type and mutant populations中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterOPUS:Study design Primary endpointOverall confirmed response rate(as assessed by independent review)Secondary endpointsPFS time OS time Rate of curative surgery for metastases SafetyERBITUX+FOLFOX4a400 mg/m2 initial IV infusion(day 1)then 250 mg/m2 weekly+oxaliplatin 85 mg/m2+5-FU/LV every 2 weeksFOLFOX4aOxaliplatin 85 mg/m2+5-FU/LV every 2 weeksEGFR-detectablemCRCRStratification by:ECOG PS 0/1,2 Bokemeyer C,et al.J Clin Oncol 2021;26(Suppl.abstract 4000)aTreatment until progression,symptomatic deterioration or unacceptable toxicity中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterKRAS evaluable population233(69%)subjects:KRAS evaluable population134(58%)KRAS wild-type99(42%)KRAS mutantGroup A:52(53%)Group B:47(47%)337 subjects(ITT)Group A:61(46%)Group B:73(54%)FOLFOXERBITUX+FOLFOX Bokemeyer C,et al.J Clin Oncol 2021;26(Suppl.abstract 4000)中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterKRAS wild-type:n=134(58%)KRAS mutant:n=99(42%)p=0.011p=0.16Role of KRAS status in response rate Bokemeyer C,et al.J Clin Oncol 2021;26(Suppl.abstract 4000)37614933中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterRelating KRAS status to efficacySecondary endpoint:PFS KRAS wild-type0.51.00.40.30.20.10.00.60.70.80.9802461012MonthsKRAS wild-type:HR=0.57;p=0.016 mPFS ERBITUX+FOLFOX:7.7 monthsmPFS FOLFOX:7.2 monthsProgression-free survival estimateFOLFOXERBITUX+FOLFOX Bokemeyer C,et al.J Clin Oncol 2021;26(Suppl.abstract 4000)中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterRelating KRAS status to efficacySecondary endpoint:PFS KRAS mutantKRAS mutant HR=1.83;p=0.0192 mPFS ERBITUX+FOLFOX:5.5 monthsmPFS FOLFOX:8.6 monthsFOLFOXERBITUX+FOLFOX0.51.00.40.30.20.10.00.60.70.80.9802461012MonthsProgression-free survival estimate Bokemeyer C,et al.J Clin Oncol 2021;26(Suppl.abstract 4000)中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterRelating KRAS status to efficacy:Progression-free survival0.51.00.40.30.20.10.00.60.70.80.9802461012PFS estimateTime(months)ERBITUX+FOLFOX wild-typeERBITUX+FOLFOX mutant0.51.00.40.30.20.10.00.60.70.80.9802461012Time(months)FOLFOX wild-typeFOLFOX mutantERBITUX+FOLFOX HR=0.45;p=0.0009 mPFS Cet+FOLFOX wild-type(n=61):7.7 monthsmPFS Cet+FOLFOX mutant(n=52):5.5 monthsFOLFOX HR=1.40;p=0.1655 mPFS FOLFOX wild-type(n=73):7.2 monthsmPFS FOLFOX mutant(n=47):8.6 monthsPFS estimate Bokemeyer C,et al.J Clin Oncol 2021;26(Suppl.abstract 4000)中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterMost common grade 3/4 AEsKRAS wild-typeKRAS mutantAdverse event,%FOLFOX(n=73)ERBITUX+FOLFOX(n=61)FOLFOX(n=47)ERBITUX+FOLFOX(n=52)Any Neutropenia Febrile neutropenia 63.032.91.483.641.0078.744.74.367.325.00Diarrhea5.511.512.85.8Peripheral sensory neuropathy8.24.92.13.8Acne-like rasha014.8011.5Infusion-related reactions01.407.7aThere was no grade 4 acne-like rash Bokemeyer C,et al.J Clin Oncol 2021;26(Suppl.abstract 4000)中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterConclusions:OPUS studyThe addition of ERBITUX to FOLFOX increased the response rate by 10%(46%vs 36%)In patients with KRAS wild-type tumors,addition of ERBITUX to FOLFOX resulted in a significant and relevant improvement in:Response rate(61%vs 37%;p=0.011)PFS(HR=0.57;p=0.016)中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer Center1.Van Cutsem E,et al.J Clin Oncol 2021;26(Abstract No.2);2.Bokemeyer C,et al.J Clin Oncol 2021;26(Abstract No.4000)ERBITUX+CT in KRAS wild-type:Consistent resultsResponse rate(%)5937010203040506070CRYSTAL1(n=348)OPUS2(n=134)4361FOLFIRIFOLFOXERBITUX+FOLFIRIERBITUX+FOLF0XCRYSTALKRAS wild-type:HR=0.68p=0.01732%risk reductionfor progressionOPUSKRAS wild-type:HR=0.57p=0.01643%risk reductionfor progression0.00.10.20.30.40.50.60.70.80.91.0024681012141618Time(months)PFS estimate0.00.10.20.30.40.50.60.70.80.91.0024681012Time(months)PFS estimate中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterERBITUX in pretreated mCRC中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterEvidence of correlation between KRAS wild-type and EGFR inhibitor efficacy in chemorefractory CRC:ResponseReference Treatment No.of patients(wild-type:mutant)Objective response,n(%)Wild-typeMutantLivre A,et al.(J Clin Oncol 2008)ERBITUX CT114(78:36)34(44)0(0)Benvenuti S,et al.(Cancer Res 2007)Panitumumab or ERBITUX or ERBITUX+CT48(32:16)10(31)1(6)DeRoock W,VanCutsem E,Tejpar S et al.(Ann Onc 2008)ERBITUX or ERBITUX+irinotecan113(67:46)27(41)0(0)Finocchiaro G et al.(ASCO Proceedings 2007)ERBITUX CT81(49:32)13(26)2(6)Di Fiore F et al.(Br J Cancer 2007)ERBITUX+CT59(43:16)12(28)0(0)Khambata-Ford S et al.(J Clin Oncol 2007)ERBITUX80(50:30)5(10)0(0)Amado R,Van Cutsem E et al.(J Clin Oncol 2008)Panitumumab208(124:84)21(17)0(0)NCIC CTG CO.17 Karapetis C,et al.WCGIC 2021 June 28 10:45 Session XVII中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterRole of KRAS mutations in predicting response,progression-free survival and overall survival in irinotecan-refractory patients treated with cetuximab plus irinotecan for a metastatic colorectal cancer:Analysis of 281 individual data from published seriesAbstract O-018 World Congress GI Cancer Barcelona 2021Di Fiore F(1),Van Cutsem E(1),Laurent-Puig P(2),Siena S(3),Frattini M(4),De Roock W(1),Lievre A(2),Sartore-Bianchi A(3),Bardelli A(5),Tejpar S(1)(1)Digestive Oncology Unit,University Hospital Gasthuisberg,Leuven-Belgium;(2)Institut National de la Sant et de la Recherche Mdicale U775,Universit Paris-Descartes,Paris-France;(3)Divisione Oncologia Medica Falck,Ospedale Niguarda Ca Granda,Milan-Italy;(4)Institute Of Pathology,Locarno-Switzerland;(5)Laboratory of Molecular Genetics Institute for Cancer Research and Treatment,University of Torino Medical School,Torino-Italy中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterResponsenKRAS mutation(n)KRAS WT(n)Complete response(CR)30(0)3(1.6)Partial response(PR)740(0)74(40.6)Stable disease(SD)10741(41.4)66(36.3)Progressive disease(PD)9758(58.6)39(21.5)Response to cetuximab-Irinotecan according to KRAS status(n=281)Di Fiore F,Van Cutsem E et al,WCGIC Barcelona,Ann Oncol,2021 abstract O-018Meta-analysis in chemorefractory CRC中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer Center6Meta-analysis in chemorefractory CRCPFS according to KRAS statusDi Fiore F,Van Cutsem E et al,WCGIC Barcelona,Ann Oncol,2021 abstract O-018中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterMeta-analysis in chemorefractory CRC OS according to KRAS statusDi Fiore F,Van Cutsem E et al,WCGIC Barcelona,Ann Oncol,2021 abstract O-018中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterOverall survival according to KRAS mutation and skin toxicityTime(months)1.000.750.500.250.000102030p=0.000815.6 months(95%CI:10.922)10.7 months(95%CI:8.316.3)5.6 months(95%CI:2.810.6)Survival probability2 good prognostic factors(wild-type and grade 2/3 skin toxicity)0 good prognostic factors(KRAS mutant and grade 0/1 skin toxicity)1 good prognostic factor(wild-type or grade 2/3 skin toxicity)Livre A,et al.J Clin Oncol 2021中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterNCIC CO.17:randomized phase III trialEGFR testing by IHC Disease progression orUnacceptable toxicityStratification:Center ECOG PS(0 or 1 vs 2)REGISTERRANDOMI ZE1:1ERBITUX+BSCBSC aloneFailed or intolerant to all recommended therapiesJonker D,et al.N Engl J Med 2021中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterERBITUX+BSCCENSOREDBSCCENSOREDSubjects at riskERBITUX+BSC 2872171367837144000BSC285197854426128210Proportion alive00.10.20.30.40.50.60.70.80.91.0Months0369121518212427 HR 0.77(95%CI:0.64,0.92)Stratified log-rank p=0.0046Study armMS95%CIERBITUX+BSC6.1 months5.4,6.7BSC alone4.6 months4.2,4.9Jonker D,et al.N Engl J Med 2021NCIC CTG CO.17:Overall Survival中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterERBITUX+BSCCENSOREDBSCCENSOREDProportion progression-free00.10.20.30.40.50.60.70.80.91.0Months03691215 HR 0.68(95%CI:0.570.80)Stratified log-rank p0.0001Study armMed PFS95%CIERBITUX+BSC1.9 months1.8,2.1BSC alone1.8 months1.8,1.9Jonker D,et al.N Engl J Med 2021NCIC CTG CO.17:Progression Free Survival 中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterNCIC CTG CO.17 K-Ras AnalysisGenomic DNA extracted from FFPET slides or sectionsAssessed by bidirectional sequencing for codon 12/13 mutationsNo difference between K-ras mutated and WT patients re:demographics,previous treatment or other variablesN=572 randomized:ITT subsetN=394:K-ras assessed subset(69%)N=164(42%)N=164(42%)mutantmutantN=230(58%)N=230(58%)wild-typewild-typeKarapetis C et al,WCGIC Barcelona,2021中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterNCIC CTG C0.17:PFS in the Mutant NCIC CTG C0.17:PFS in the Mutant K-ras K-ras SubgroupSubgroupHR 0.99 HR 0.99 95%CI (0.73,1.35)95%CI (0.73,1.35)Log rank p-value:Log rank p-value:0.960.96Study armStudy armMed PFS Med PFS(months)(months)95%CI95%CICetuximab+BSCCetuximab+BSC1.81.81.7 1.81.7 1.8BSC aloneBSC alone1.81.81.7 1.81.7 1.8Karapetis C et al,WCGIC Barcelona,2021中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterNCIC CTG C0.17:PFS in the NCIC CTG C0.17:PFS in the K-rasK-ras Wild-Type Wild-Type PatientsPatientsHR 0.40 HR 0.40 95%CI (0.30,0.54)95%CI (0.30,0.54)Log rank p-value:Log rank p-value:0.00010.0001Study armStudy armMed PFS Med PFS(months)(months)95%CI95%CICetuximab+BSCCetuximab+BSC3.83.83.1 5.13.1 5.1BSC aloneBSC alone1.91.91.8 2.01.8 2.0Karapetis C et al,WCGIC Barcelona,2021中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterNCIC CTG C0.17:Overall survival in NCIC CTG C0.17:Overall survival in K-rasK-ras Mutant patientsMutant patientsHR 0.98 HR 0.98 95%CI (0.70,1.37)95%CI (0.70,1.37)Log rank p-value:Log rank p-value:0.890.89Study armStudy armMS(months)MS(months)95%CI95%CICetuximab+BSCCetuximab+BSC4.54.53.8 5.63.8 5.6BSC aloneBSC alone4.64.63.6 5.53.6 5.5Karapetis C et al,WCGIC Barcelona,2021中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterNCIC CTG C0.17:Overall survival in NCIC CTG C0.17:Overall survival in K-rasK-ras Wild-Type patientsWild-Type patientsHR 0.55HR 0.55 95%CI (0.41,0.74)95%CI (0.41,0.74)Log rank p-value:Log rank p-value:0.000110m中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterConclusionsKRAS is the first molecular marker used to select a targeted therapy in combination with a standard chemotherapy regimenERBITUX brings a new era of tailored therapy to treatment of mCRCERBITUX in combination with a standard first-line treatment for patients with mCRC is an important new option in patients with KRAS wild-type tumors中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer Center主要内容主要内容以分子指以分子指标为指指导的靶向治的靶向治疗时代的来代的来临多个靶向多个靶向药物物联合的重新定位合的重新定位靶向靶向药物治物治疗的广泛研究的广泛研究中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterInterim results from PACCE irinotecan+bevacizumab panitumumab for first-line treatment of mCRC study designHecht J,et al.Abstract 279SCREENINGRANDOMIZEOx-based CT(e.g.FOLFOX)N=800 inv choiceIn-based CT(e.g.FOLFIRI)N=200inv choicePanitumumab6mg/kg Q2WOx-CTBevacizumabPanitumumab6 mg/kg Q2WIri-CTBevacizumabOx-CTBevacizumabIri-CTBevacizumab1:11:1中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterInterim results from PACCE irinotecan+bevacizumab+/-panitumumab for first-line treatment of mCRC median PFS(central review)Hecht J,et al.Abstract 279100806040200PFS(%)0510152025Time(days)Panitumumab+Bevacizumab/Iri-CTBevacizumab/Iri-CT*PFS events(%)Median(95%CI months54(47)10.1(8.213.1)43(37)11.1(9.013.2)HR=1.2(95%CI:0.801.82)*Descriptive onlyBACK中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterInterim results from PACCE irinotecan+bevacizumab panitumumab for first-line treatment of mCRC response by KRAS statusHecht J,et al.Abstract 279NPmab+Bev/iri-CTn/N(%)Bev/iri-CTn/N(%)Odds ratio(95%CI)Wild-type KRAS115 31/57(54)27/58(47)1.42(0.633.21)Mutant KRAS 85 14/46(30)15/39(38)0.59(0.231.55)BACK中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer Center0510152025Interim results from PACCE oxaliplatin+bevacizumab+/-panitumumab for first-line treatment of mCRC PFS(central review)Hecht JR,et al.Abstract 273100806040200PFSevents(%)Median(95%CI)monthspmab+bev/Ox-CT599.6(8.810.9)bev/Ox-CT5211.1(10.311.9)HR=1.27(95%CI:1.051.53)*Descriptive onlyTime(months)PFS(%)BACK中中中中 山山山山 大大大大 学学学学 肿肿肿肿 瘤瘤瘤瘤 医医医医 院院院院Sun Yat-sen University Cancer CenterSun Yat-sen University Cancer CenterSurviving(%)Interim results from PACCE oxaliplatin+bevacizumab+/-panitumumab for first-line treatment of mCRC OS(central review)Hecht JR,et al.Abst