治疗BRAF突变的不可切除或转移性黑色素瘤的新药物组合:encorafenib和binimetinib
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摘要
encorafenib和binimetinib是由Array生物制药公司开发的鼠类肉瘤滤过性毒菌致癌性同源体B1(BRAF)抑制剂和丝裂原活化胞外信号调控激酶(MEK)抑制剂。2018年6月27日,美国食品和药物管理局批准encorafenib和binimetinib联合应用治疗BRAF V600E或V600K突变的不可切除或转移性黑色素瘤。本文主要介绍其作用机制、药动学、临床研究及安全性。
Encorafenib is a kinase inhibitor that targets v-raf murine sarcoma viral oncogene homolog B1( BRAF) and binimetinib is a inhibitor of mitogen-activated extracellular signal regulated kinase( MEK)activity, both of them were developed by Array Biopharma Inc. Encorafenib and binimetinib in combination was approved for unresectable or metastatic melanoma with a BRAF V600E or V600K mutation by the U.S. Food and Drug Administration on June 27, 2018. The mechanism, pharmacokinetics, clinical research and safety of encorafenib and binimetinib in combination were reviewed in this article.
Encorafenib is a kinase inhibitor that targets v-raf murine sarcoma viral oncogene homolog B1( BRAF) and binimetinib is a inhibitor of mitogen-activated extracellular signal regulated kinase( MEK)activity, both of them were developed by Array Biopharma Inc. Encorafenib and binimetinib in combination was approved for unresectable or metastatic melanoma with a BRAF V600E or V600K mutation by the U.S. Food and Drug Administration on June 27, 2018. The mechanism, pharmacokinetics, clinical research and safety of encorafenib and binimetinib in combination were reviewed in this article.
引文
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[2]刘杰,朱丽萍,杨旭丽,等.2014年中国皮肤黑色素瘤发病与死亡分析[J].中国肿瘤,2018,27(4):241-245.
[3]de SANTIS CE,LIN CC,MARIOTTO AB,et al.Cancer treatment and survivorship statistics,2014[J].CA Cancer J Clin,2014,64(4):252-271.
[4]LIU Q,DAS M,LIU Y,et al.Targeted drug delivery to melanoma[J].Adv Drug Deliv Rev,2018,127:208-221.
[5]FDA.BRAFTOVITM(encorafenib)[EB/OL].(2018-06-28)[2018-07-04].https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210496lbl.pdf.
[6]FDA.MEKTOVI誖(binimetinib)[EB/OL].(2018-06-28)[2018-07-04].https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210498lbl.pdf.
[7]FDA.FDA approves encorafenib and binimetinib in combination for unresectable or metastatic melanoma with BRAF mutations[EB/OL].(2018-06-27)[2018-07-04].https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm611981.htm.
[8]PANEK RL,LU GH,KLUTCHKO SR,et al.In vitro pharmacological characterization of PD 166285,a new nanomolar potent and broadly active protein tyrosine kinase inhibitor[J].J Pharmacol Exp Ther,1997,283(3):1433-1444.
[9]李靖,傅国芬.治疗转移性黑色素瘤新药达拉菲尼[J].中国新药与临床杂志,2014,33(11):785-787.
[10]BUCHEIT AD,SYKLAWER E,JAKOB JA,et al.Clinical characteristics and outcomes with specific BRAF and NRASmutations in patients with metastatic melanoma[J].Cancer,2013,119(21):3821-3829.
[11]ASCIERTO PA,KIRKWOOD JM,GROB JJ,et al.The role of BRAF V600 mutation in melanoma[J].J Transl Med,2012,10(1):85.
[12]RAJAGOPALAN H,BARDELLI A,LENGAUER C,et al.Tumorigenesis:RAF/RAS oncogenes and mismatch-repair status[J].Nature,2002,418(6901):934.
[13]SOSMAN JA,KIM KB,SCHUCHTER L,et al.Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib[J].N Engl J Med,2012,366(8):707-714.
[14]PARAISO KH,FEDORENKO IV,CANTINI LP,et al.Recovery of phospho-ERK activity allows melanoma cells to escape from BRAF inhibitor therapy[J].Br J Cancer,2010,102(12):1724-1730.
[15]TRUNZER K,PAVLICK AC,SCHUCHTER L,et al.Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma[J].J Clin Oncol,2013,31(14):1767-1774.
[16]DELORD JP,ROBERT C,NYAKAS M,et al.Phase I doseescalation and-expansion study of the BRAF inhibitor encorafenib(LGX818)in metastatic BRAF-mutant melanoma[J].Clin Cancer Res,2017,23(18):5339-5348.
[17]ASCIERTO PA,SCHADENDORF D,BERKING C,et al.MEK162 for patients with advanced melanoma harbouring NRASor Val600 BRAF mutations:a non-randomised,open-label phase 2 study[J].Lancet Oncol,2013,14(3):249-256.
[18]FDA.New drug application approval(NDA 210498)[EB/OL].(2018-06-27)[2018-07-06].https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2018/210498orig1s000ltr.pdf.
[19]ASCIERTO PA,MARINCOLA FM,ATKINS MB.What's new in melanoma?Combination![J].J Transl Med,2015,13:213.
[20]EROGLU Z,RIBAS A.Combination therapy with BRAF and MEK inhibitors for melanoma:latest evidence and place in therapy[J].Ther Adv Med Oncol,2016,8(1):48-56.
[21]NIH.Study comparing combination of LGX818 plus MEK162versus vemurafenib and LGX818 monotherapy in BRAF mutant melanoma(COLUMBUS)[EB/OL].(2018-03-21)[2018-07-09].https://clinicaltrials.gov/ct2/show/NCT01909453?term=NCT01909453&rank=1.
[22]DUMMER R,ASCIERTO PA,GOGAS HJ,et al.Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma(COLUMBUS):a multicentre,open-label,randomised phase 3 trial[J].Lancet Oncol,2018,19(5):603-615.
[23]DUMMER R,ASCIERTO PA,GOGAS HJ,et al.12150 results of COLUMBUS part 2:a phase 3 trial of encorafenib(ENCO)plus binimetinib(BINI)versus ENCO in BRAF-mutant melanoma[J].Ann Oncol,2017,28(Suppl5):429-430.
[24]NIH.Open label,multicentre study of encorafenib+binimetinib+PD(programmed cell death protein)-1 antibody pembrolizumab(IMMU-TARGET)[EB/OL].(2018-05-09)[2018-07-09].https://clinicaltrials.gov/ct2/show/NCT02902042?term=encorafenib+binimetinib&cond=Melanoma&rank=4.
[25]NIH.Immunotherapy with ipilimumab and nivolumab preceded or not by a targeted therapy with encorafenib and binimetinib(EBIN)[EB/OL].(2017-09-05)[2018-07-09].https://clinicaltrials.gov/ct2/show/NCT03235245?term=encorafenib+binimetinib&cond=Melanoma&rank=1.