肝细胞癌的靶向及免疫治疗进展

魏建莹; 孙巍; 刘晓民; 陈京龙

doi:10.3969/j.issn.1001-5256.2020.10.035

肝细胞癌的靶向及免疫治疗进展

DOI: 10.3969/j.issn.1001-5256.2020.10.035

首都医科大学附属北京地坛医院肿瘤内科

详细信息

中图分类号: R735.7
计量
- 文章访问数: 815
- HTML全文浏览量: 27
- PDF下载量: 149
- 被引次数: 0
出版历程
- 收稿日期: 2020-03-17
- 出版日期: 2020-10-20

Advances in targeted therapy and immunotherapy for hepatocelluar carcinoma

Department of Oncology,Beijing Ditan Hospital,Capital Medical University

摘要

摘要: 当前肝细胞癌的发病率及病死率居高不下,全身系统性治疗在晚期肝细胞癌治疗中发挥重要作用。主要叙述了分子靶向药物、免疫检查点抑制剂在肝细胞癌中的应用。指出当前肝细胞癌治疗的研究热点主要在双靶向、双免疫、靶向与免疫联合治疗。
- 癌,肝细胞 /
- 分子靶向治疗 /
- 免疫疗法
Abstract: There are still high incidence and mortality rates of hepatocellular carcinoma at present,and systemic treatment plays an important role in the treatment of advanced hepatocellular carcinoma. This article describes the application of molecular-targeted drugs and immune checkpoint inhibitors in hepatocellular carcinoma and points out that dual-targeted therapy,dual immunotherapy,and targeted therapy combined with immunotherapy are the current research hotspots in the treatment of hepatocellular carcinoma.
- carcinoma,hepatocellular /
- molecular targeted therapy /
- immunotherapy

HTML全文

参考文献(41)

[1] FERLAY J,SOERJOMATARAM I,DIKSHIT R,et al. Cancer incidence and mortality worldwide:Sources, methods and major patterns in GLOBOCAN 2012[J]. Int J Cancer,2015,136(5):e359-e386.

[2] RYERSON AB,EHEMAN CR,ALTEKRUSE SF,et al. Annual Report to the Nation on the Status of Cancer,1975-2012,featuring the increasing incidence of liver cancer[J]. Cancer,2016,122(9):1312-1337.

[3] MCGLYNN KA,PETRICK JL,LONDON WT. Global epidemiology of hepatocellular carcinoma:An emphasis on demographic and regional variability[J]. Clin Liver Dis,2015,19(2):223-238.

[4] LLOVET JM,RICCI S,MAZZAFERRO V,et al. Sorafenib in advanced hepatocellular carcinoma[J]. N Engl J Med,2008,359(4):378-390.

[5] CHENG AL,KANG YK,CHEN Z,et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma:A phase III randomised,doubleblind,placebo-controlled trial[J]. Lancet Oncol,2009,10(1):25-34.

[6] CHENG AL,KANG YK,LIN DY,et al. Sunitinib versus sorafenib in advanced hepatocellular cancer:Results of a randomized phase III trial[J]. J Clin Oncol,2013,31(32):4067-4075.

[7] JOHNSON PJ,QIN S,PARK JW,et al. Brivanib versus sorafenib as first-line therapy in patients with unresectable,advanced hepatocellular carcinoma:Results from the randomized phase III BRISK-FL study[J]. J Clin Oncol,2013,31(28):3517-3524.

[8] ZHU AX,ROSMORDUC O,EVANS TR,et al. SEARCH:A phase III,randomized,double-blind,placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma[J]. J Clin Oncol,2015,33(6):559-566.

[9] CAINAP C,QIN S,HUANG WT,et al. Linifanib versus Sorafenib in patients with advanced hepatocellular carcinoma:Results of a randomized phase III trial[J]. J Clin Oncol,2015,33(2):172-179.

[10] VILGRAIN V,PEREIRA H,ASSENAT E,et al. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma(SARAH):An open-label randomised controlled phase 3 trial[J]. Lancet Oncol,2017,18(12):1624-1636.

[11] KUDO M,UESHIMA K,YOKOSUKA O,et al. Sorafenib plus low-dose cisplatin and fluorouracil hepatic arterial infusion chemotherapy versus sorafenib alone in patients with advanced hepatocellular carcinoma(SILIUS):A randomised,open label,phase 3 trial[J]. Lancet Gastroenterol Hepatol,2018,3(6):424-432.

[12] CHOW P,GANDHI M,TAN SB,et al. SIRveNIB:Selective internal radiation therapy versus Sorafenib in Asia-Pacific patients with hepatocellular carcinoma[J]. J Clin Oncol,2018,36(19):1913-1921.

[13] ABOU-ALFA GK,QIN S,RYOO BY,et al. Phase III randomized study of second line ADI-PEG 20 plus best supportive care versus placebo plus best supportive care in patients with advanced hepatocellular carcinoma[J]. Ann Oncol,2018,29(6):1402-1408.

[14] KUDO M,FINN RS,QIN S,et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma:A randomised phase 3 non-inferiority trial[J]. Lancet,2018,391(10126):1163-1173.

[15] IKEDA K,KUDO M,KAWAZOE S,et al. Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma[J]. J Gastroenterol,2017,52(4):512-519.

[16] WILHELM SM,DUMAS J,ADNANE L,et al. Regorafenib(BAY73-4506):A new oral multikinase inhibitor of angiogenic,stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity[J]. Int J Cancer,2011,129(1):245-255.

[17] ABOU-ELKACEM L,ARNS S,BRIX G,et al. Regorafenib inhibits growth,angiogenesis,and metastasis in a highly aggressive,orthotopic colon cancer model[J]. Mol Cancer Ther,2013,12(7):1322-1331.

[18] BRUIX J,QIN S,MERLE P,et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment(RESORCE):A randomised,double-blind,placebo-concrolled, phase 3 trial[J]. Lancet, 2017, 389(10064):56-66.

[19] XIANG Q,CHEN W,REN M,et al. Cabozantinib suppresses tumor growth and metastasis in hepatocellular carcinoma by a dual blockade of VEGFR2 and MET[J]. Clin Cancer Res,2014,20(11):2959-2970.

[20] YAKES FM,CHEN J,TAN J,et al. Cabozantinib(XL184),a novel MET and VEGFR2 inhibitor,simultaneously suppresses metastasis,angiogenesis,and tumor growth[J]. Mol Cancer Ther,2011,10(12):2298-2308.

[21] ABOU-ALFA GK,MEYER T,CHENG AL,et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma[J]. N Engl J Med,2018,379(1):54-63.

[22] SPRATLIN JL,COHEN RB,EADENS M,et al. Phase I pharmacologic and biologic study of ramucirumab(IMC-1121B),a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2[J]. J Clin Oncol,2010,28(5):780-787.

[23] ZHU AX,FINN RS,MULCAHY M,et al. A phase II and biomarker study of ramucirumab,a human monoclonal antibody targeting the VEGF receptor-2,as first-line monotherapy in patients with advanced hepatocellular cancer[J]. Clin Cancer Res,2013,19(23):6614-6623.

[24] ZHU AX,PARK JO,RYOO BY,et al. Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib(REACH):A randomised,double-blind,multicentre,phase 3 trial[J]. Lancet Oncol,2015,16(7):859-870.

[25] KUDO M,HATANO E,OHKAWA S,et al. Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma:Japanese subgroup analysis of the REACH trial[J]. J Gastroenterol,2017,52(4):494-503.

[26] PARK JO,RYOO BY,YEN CJ,et al. Second-line ramucirumab therapy for advanced hepatocellular carcinoma(REACH):An East Asian and non-East Asian subgroup analysis[J]. Oncotarget,2016,7(46):75482-75491.

[27] ZHU AX,KANG YK,YEN CJ,et al. Ramucirumab in advanced hepatocellular carcinoma and elevated alpha-fetoprotein following sorafenib(REACH-2):A randomised,double-blind,placebocontrolled phase 3 trial[J]. Lancet Oncol,2019.[Online ahead of print]

[28] EL-KHOUEIRY AB,SANGRO B,YAU T,et al. Nivolumab in patients with advanced hepatocellular carcinoma(CheckMate040):An open-label,non-comparative,phase 1/2 dose escalation and expansion trial[J]. Lancet, 2017, 389(10088):2492-2502.

[29] ZHU AX,FINN RS,EDELINE J,et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib(KEYNOTE-224):A non-randomised,open-label phase 2 trial[J]. Lancet Oncol,2018,19(7):940-952.

[30] SANGRO B,GOMEZ-MARTIN C,de la MATA M,et al. A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C[J]. J Hepatol,2013,59(1):81-88.

[31] DUFFY AG,ULAHANNAN SV,MAKOROVA-RUSHER O,et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma[J]. J Hepatol,2017,66(3):545-551.

[32] MO H,HUANG J,XU J,et al. Safety,anti-tumour activity,and pharmacokinetics of fixed-dose SHR-1210,an anti-PD-1 antibody in advanced solid tumours:A dose-escalation,phase 1study[J]. Br J Cancer,2018,119(5):538-545.

[33] FANG W,YANG Y,MA Y,et al. Camrelizumab(SHR-1210)alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma:Results from two single-arm,phase 1 trials[J]. Lancet Oncol,2018,19(10):1338-1350.

[34] QIN S,REN Z,MENG Z,et al. Camrelizumab in patients with previously treated advanced hepatocellular carcinoma:A multicentre,open-label,parallel-group,randomised,phase 2trial[J]. Lancet Oncol,2020,21(4):571-580.

[35] QIN S,FINN RS,KUDO M,et al. RATIONALE 301 study:Tislelizumab versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma[J]. Future Oncol,2019,15(16):1811-1822.

[36] STEIN S,PISHVAIAN MJ,LEE MS,et al. Safety and clinical activity of 1L atezolizumab+bevacizumab in a phase Ib study in hepatocellular carcinoma(HCC)[J]. J Clin Oncol,2018.[Online ahead of print]

[37] FINN RS,QIN S,IKEDA M,et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma[J]. N Engl J Med,2020,382(20):1894-1905.

[38] KASEB AO,MORRIS JS,IWASAKI M,et al. Phase II trial of bevacizumab and erlotinib as a second-line therapy for advanced hepatocellular carcinoma[J]. Onco Targets Ther,2016,9:773-780.

[39] HE L,DENG H,LEI J,et al. Efficacy of bevacizumab combined with erlotinib for advanced hepatocellular carcinoma:A single-arm meta-analysis based on prospective studies[J]. BMC Cancer,2019,19(1):276.

[40] MAKKER V,RASCO D,VOGELZANG NJ,et al. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer:An interim analysis of a multicentre,open-label,single-arm,phase 2 trial[J]. Lancet Oncol,2019,20(5):711-718.

[41] HERBST RS,ARKENAU HT,SANTANA-DAVILA R,et al.Ramucirumab plus pembrolizumab in patients with previously treated advanced non-small-cell lung cancer,gastro-oesophageal cancer,or urothelial carcinomas(JVDF):A multicohort,non-randomised,open-label,phase 1a/b trial[J].Lancet Oncol,2019,20(8):1109-1123.

施引文献

资源附件(0)

访问统计