BRAF突变晚期结直肠癌的治疗进展
摘要
近年来,对于结直肠癌分子分型的研究越来越深入,有丝分裂原活化蛋白激酶(mitogen-activated protein kinases,MAPK)通路上的V-raf鼠肉瘤病毒癌基因同源体B(V-raf murine sarcoma viral oncogene homolog,BRAF)作为该通路上重要的效应分子,在结直肠癌的发生和发展中起着举足轻重的作用。临床观察发现,携带BRAF V600E突变的结直肠癌患者预后劣于BRAF野生型患者,对传统药物的敏感性也存在较大的差异。故针对BRAF突变晚期结直肠癌的治疗策略,本文主要从化学治疗、靶向治疗及免疫治疗3个方面进行详细阐述。
引文
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[14]Cremolini C,Loupakis F,Antoniotti C,et al.FOLFOXI-RI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer:updated overall survival and molecular subgroup analyses of the open-label,phase 3 TRIBE study[J].Lancet Oncol,2015,16(13):1306-1315.
[15]Flaherty KT,Puzanov I,Kim KB,et al.Inhibition of mutated,activated BRAF in metastatic melanoma[J].NEngl J Med,2010,363(9):809-819.
[16]Kopetz S,Desai J,Chan E,et al.PhaseⅡpilot study of vemurafenib in patients with metastatic BRAF-mutated colorectal cancer[J].J Clin Oncol,2015,33(34):4032-4038.
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[23]Corcoran RB,Ebi H,Turke AB,et al.EGFR-mediated reactivation of MAPK signaling contributes to insensitivity of BRAF-mutant colorectal cancers to RAF inhibition with vemurafenib[J].Cancer Discov,2012,2(3):227-235.
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[25]Huijberts S,Schellens JHM,Fakih M,et al.BEACONCRC(binimetinib[BINI],encorafenib[ENCO],and cetuximab[CTX]combined to treat BRAF-mutant metastatic colorectal cancer[m CRC]):A multicenter,randomized,open-label,three-arm phaseⅢstudy of ENCOplus CTX plus or minus BINI vs irinotecan[J].J Clin Oncol,2017,35(suppl 15):TPS3622.
[26]Van Cutsem E,Cuyle P,Huijberts S,et al.O-027BEACON CRC study safety lead-in:Assessment of the BRAF inhibitor encorafenib+MEK inhibitor binimetinib+anti-epidermal growth factor receptor antibody cetuximab for BRAFV600E metastatic colorectal cancer[J].Ann Oncol,2018,29(suppl 5):627.
[27]Mao M,Tian F,Mariadason JM,et al.Resistance to BRAF inhibition in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents[J].Clin Cancer Res,2013,19(3):657-667.
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[29]Tabernero J,Van GR,Guren TK,et al.Phase 2 results:Encorafenib(ENCO)and cetuximab(CETUX)with or without alpelisib(ALP)in patients with advanced BRAF-mutant colorectal cancer(BRAFm CRC)[J].JClin Oncol,2016,34(suppl 15):3544.
[30]Hazar-Rethinam M,Kleyman M,Han GC,et al.Convergent therapeutic strategies to overcome the heterogeneity of acquired resistance in BRAFV600E colorectal cancer[J].Cancer Discov,2018,8(4):417-427.
[2]Maughan TS,Adams RA,Smith CG,et al.Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer:results of the randomised phase 3 MRC COIN trial[J].Lancet,2011,377(9783):2103-2114.
[3]Gonsalves WI,Mahoney MR,Sargent DJ,et al.Patient and tumor characteristics and BRAF and KRAS mutations in colon cancer,NCCTG/Alliance N0147[J].J Natl Cancer Inst,2014,106(7):1-8.
[4]Clancy C,Burke JP,Kalady MF,et al.BRAF mutation is associated with distinct clinicopathological characteristics in colorectal cancer:a systematic review and meta-analysis[J].Color Dis,2013,15(12):e711-718.
[5]Yaeger R,Cercek A,Chou JF,et al.BRAF mutation predicts for poor outcomes after metastasectomy in patients with metastatic colorectal cancer[J].Cancer,2014,120(15):2316-2324.
[6]Samowitz WS,Sweeney C,Herrick J,et al.Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers[J].Cancer Res,2005,65(14):6063-6069.
[7]Seligmann JF,Fisher D,Smith CG,et al.Investigating the poor outcomes of BRAF-mutant advanced colorectal cancer:Analysis from 2530 patients in randomised clinical trials[J].Ann Oncol,2017,28(3):562-568.
[8]Karapetis CS,Khambata-Ford S,Jonker DJ,et al.K-ras mutations and benefit from cetuximab in advanced colorectal cancer[J].N Engl J Med,2008,359(17):1757-1765.
[9]National Comprehensive Cancer Network.Clinical practice guidelines in oncology(NCCN guidelines).Colon cancer,version 1.2018[EB/OL].(2018-01-18)[2018-07-23].http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf.
[10]Pietrantonio F,Petrelli F,Coinu A,et al.Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab:A metaanalysis[J].Eur J Cancer,2015,51(5):587-594.
[11]Rowland A,Dias MM,Wiese MD,et al.Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal antibody therapy for RAS wildtype metastatic colorectal cancer[J].Br J Cancer,2015,112(12):1888-1894.
[12]Chinese Society of Clinical Oncology(CSCO)diagnosis and treatment guidelines for colorectal cancer working group.Chinese Society of Clinical Oncology(CSCO)diagnosis and treatment guidelines for colorectal cancer2018(English version)[J].Chin J Cancer Res,2019,31(1):117-134.
[13]Loupakis F,Cremolini C,Salvatore L,et al.FOLFOXIRIplus bevacizumab as first-line treatment in BRAF mutant metastatic colorectal cancer[J].Eur J Cancer,2014,50(1):57-63.
[14]Cremolini C,Loupakis F,Antoniotti C,et al.FOLFOXI-RI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer:updated overall survival and molecular subgroup analyses of the open-label,phase 3 TRIBE study[J].Lancet Oncol,2015,16(13):1306-1315.
[15]Flaherty KT,Puzanov I,Kim KB,et al.Inhibition of mutated,activated BRAF in metastatic melanoma[J].NEngl J Med,2010,363(9):809-819.
[16]Kopetz S,Desai J,Chan E,et al.PhaseⅡpilot study of vemurafenib in patients with metastatic BRAF-mutated colorectal cancer[J].J Clin Oncol,2015,33(34):4032-4038.
[17]Hyman DM,Puzanov I,Subbiah V,et al.Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations[J].N Engl J Med,2015,373(8):726-736.
[18]Gomez-Roca CA,Delord J,Robert C,et al.Encorafenib(LGX818),an oral BRAF inhibitor,in patients(pts)with BRAF V600E metastatic colorectal cancer(m CRC):results of dose expansion in an open-label,phase 1 study[J].Ann Oncol,2014,25(suppl 4):iv182-183.
[19]Yang H,Higgins B,Kolinsky K,et al.Antitumor activity of BRAF inhibitor vemurafenib in preclinical models of BRAF-mutant colorectal cancer[J].Cancer Res,2012,72(3):779-789.
[20]Hong DS,Morris VK,El Osta B,et al.PhaseⅠB study of vemurafenib in combination with irinotecan and cetuximab in patients with metastatic colorectal cancer with BRAFV600E mutation[J].Cancer Discov,2016,6(12):1352-1365.
[21]Kopetz S,McDonough SL,Morris VK,et al.Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer(SWOG 1406)[J].J Clin Oncol,2017,35(suppl 4):520.
[22]Desai J,Markman B,Ananda S,et al.A phaseⅠ/Ⅱtrial of combined BRAF and EGFR inhibition in patients(pts)with BRAF V600E mutated(BRAFm)metastatic colorectal(m CRC):The EVi CT(Erlotinib and Vemurafenib in Combination Trial)study[J].J Clin Oncol,2017,35(suppl 15):3557.
[23]Corcoran RB,Ebi H,Turke AB,et al.EGFR-mediated reactivation of MAPK signaling contributes to insensitivity of BRAF-mutant colorectal cancers to RAF inhibition with vemurafenib[J].Cancer Discov,2012,2(3):227-235.
[24]Corcoran RB,AndréT,Atreya CE,et al.Combined BRAF,EGFR,and MEK inhibition in patients with BRAF V600E-mutant colorectal cancer[J].Cancer Discov,2018,8(4):428-443.
[25]Huijberts S,Schellens JHM,Fakih M,et al.BEACONCRC(binimetinib[BINI],encorafenib[ENCO],and cetuximab[CTX]combined to treat BRAF-mutant metastatic colorectal cancer[m CRC]):A multicenter,randomized,open-label,three-arm phaseⅢstudy of ENCOplus CTX plus or minus BINI vs irinotecan[J].J Clin Oncol,2017,35(suppl 15):TPS3622.
[26]Van Cutsem E,Cuyle P,Huijberts S,et al.O-027BEACON CRC study safety lead-in:Assessment of the BRAF inhibitor encorafenib+MEK inhibitor binimetinib+anti-epidermal growth factor receptor antibody cetuximab for BRAFV600E metastatic colorectal cancer[J].Ann Oncol,2018,29(suppl 5):627.
[27]Mao M,Tian F,Mariadason JM,et al.Resistance to BRAF inhibition in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents[J].Clin Cancer Res,2013,19(3):657-667.
[28]Van Geel RMJM,Tabernero J,Elez E,et al.A phaseⅠb dose-escalation study of encorafenib and cetuximab with or without alpelisib in metastatic BRAF-mutant colorectal cancer[J].Cancer Discov,2017,7(6):610-619.
[29]Tabernero J,Van GR,Guren TK,et al.Phase 2 results:Encorafenib(ENCO)and cetuximab(CETUX)with or without alpelisib(ALP)in patients with advanced BRAF-mutant colorectal cancer(BRAFm CRC)[J].JClin Oncol,2016,34(suppl 15):3544.
[30]Hazar-Rethinam M,Kleyman M,Han GC,et al.Convergent therapeutic strategies to overcome the heterogeneity of acquired resistance in BRAFV600E colorectal cancer[J].Cancer Discov,2018,8(4):417-427.