表皮生长因子受体靶向药物对进展期胰腺癌治疗作用的Meta分析

周子栋; 李仁礼; 陈凯; 张文成; 夏时海

doi:10.3969/j.issn.1001-5256.2020.05.029

表皮生长因子受体靶向药物对进展期胰腺癌治疗作用的Meta分析

DOI: 10.3969/j.issn.1001-5256.2020.05.029

1. 武警后勤学院
2. 武警特色医学中心消化疾病研究所
3. 武警特色医学中心肝脏胰腺纤维化与分子诊疗重点实验室

基金项目:

十三五国家重大专项课题子课题（2018ZX10732-202-004-005）；天津市科技计划项目（15ZXLCSY00040）；

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中图分类号: R735.9
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出版历程
- 出版日期: 2020-05-20

Clinical effect of epidermal growth factor receptor-targeted agents in treatment of advanced pancreatic cancer:A Meta-analysis

Logistics University of Chinese People’s Armed Police Forces, Tianjin 300309, China

Research funding:

摘要

摘要:
目的系统评价表皮生长因子受体(EGFR)靶向药物治疗进展期胰腺癌的有效性。方法利用EMbase、PubMed、Cochrane Library、Clinical Trials、中国知网、万方和维普数据库,检索EGFR靶向药物治疗进展期胰腺癌的临床随机对照试验相关文献,根据文献质量和相应标准筛选出合适的研究提取数据,并利用RevMan 5. 3和STATA 12. 0软件进行Meta分析。结果共纳入8项研究,合计2382例患者。Meta分析总的结果显示,与对照组相比,试验组不能提高胰腺癌治疗的总生存期(HR=0. 86,95%CI:074～1.02,P> 0. 05)和客观缓解率(RR=1. 00,95%CI:0. 76～1. 32,P> 0. 05),但能延长无进展生存期(HR=0. 78,95%CI:0. 62～0.98,P<0. 05)和疾病控制率(RR=1. 22,95%CI:1. 04～1. 43,P<0. 05);亚组分析显示,找到异质性来源并排除异质性较高的研究后,试验组能提高胰腺癌患者的总生存期(HR=0. 85,95%CI:0. 77～0. 94...
- 胰腺肿瘤 /
- 受体,表皮生长因子 /
- 治疗学 /
- Meta分析(主题)
Abstract:
Objective To systematically evaluate the clinical effect of epidermal growth factor receptor( EGFR)-targeted agents in the treatment of advanced pancreatic cancer.Methods EMbase, PubMed, Cochrane Library, Clinical Trials, CNKI, Wanfang Data, and VIP were searched for randomized controlled trials(RCTs) of EGFR-targeted therapies for advanced pancreatic cancer. Eligible RCTs were screened out based on quality and related criteria, and RevMan 5.3 and STATA 12.0 were used to perform the meta-analysis.Results A total of 8 RCTs were included, with 2382 patients in total. The results of the meta-analysis showed that compared with the control group,the experimental group had no increases in overall survival time(hazard ratio [HR] =0.86, 95% confidence interval [CI]: 0.74-1.02,P> 0. 05) and objective response rate(risk ratio [RR] = 1. 00, 95% CI: 0. 76-1. 32,P> 0. 05), but had significant increases in progression-free survival time(HR =0.78, 95%CI: 0.62-0.98,P< 0. 05) and disease control rate(RR = 1. 22, 95% CI: 1. 04-1. 43,P< 0. 05). The subgroup analysis showed that after the source of heterogeneity was identified and the studies with high heterogeneity were excluded, the experimental group had a significant increase in overall survival time(HR =0. 85, 95%CI: 0. 77-0. 94,P< 0. 05), and the patients with rash appeared to be more sensitive to the therapies(HR =0.70, 95%CI: 0.54-0.92,P< 0. 05).Conclusion For patients with advanced pancreatic cancer, EGFR-targeted therapies can effectively prolong overall survival time and improve quality of life.
- pancreatic neoplasms /
- receptor,epidermal growth factor /
- therapeutics /
- Meta-analysis as topic

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参考文献(34)

[1] SIEGEL R, MA J, ZOU Z, et al. Cancer statistics, 2014[J].CA Cancer J Clin, 2014, 64(1):9-29.

[2] SIEGEL RL, MILLER KD, JEMAL A. Cancer statistics, 2016[J]. CA Cancer J Clin, 2016, 66(1):7-30.

[3] SIEGEL RL, MILLER KD, JEMAL A. Cancer Statistics, 2017[J]. CA Cancer J Clin, 2017, 67(1):7-30.

[4] CHEN W, ZHENG R, BAADE PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2):115-132.

[5] CHEN W, SUN K, ZHENG R, et al. Cancer incidence and mortality in China, 2014[J]. Chin J Cancer Res, 2018, 30(1):1-12.

[6] KORC M, CHANDRASEKAR B, YAMANAKA Y, et al. Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor alpha[J]. J Clin Invest, 1992, 90(4):1352-1360.

[7] YAMANAKA Y, FRIESS H, KOBRIN MS, et al. Coexpression of epidermal growth factor receptor and ligands in human pancreatic cancer is associated with enhanced tumor aggressiveness[J]. Anticancer Res, 1993, 13(3):565-569.

[8] YAMAOKA T, OHBA M, OHMORI T. Molecular-targeted therapies for epidermal growth factor receptor and its resistance mechanisms[J]. Int J Mol Sci, 2017, 18(11):e2420.

[9] CATALDO VD, GIBBONS DL, PÉREZ-SOLER R, et al. Treatment of non-small-cel lung cancer with erlotinib or gefitinib[J]. N Engl J Med, 2011, 364(10):947-955.

[10] CITRI A, YARDEN Y. EGF-ERBB signalling:Towards the systems level[J]. Nat Rev Mol Cel Biol, 2006, 7(7):505-516.

[11] BALABAN EP, MANGU PB, KHORANA AA, et al. Locally advanced, unresectable pancreatic cancer:American Society of Clinical Oncology clinical practice guideline[J]. J Clin Oncol,2016, 34(22):2654-2668.

[12] SOHAL DP, MANGU PB, KHORANA AA, et al. Metastatic pancreatic cancer:American Society of Clinical Oncology clinical practice guideline[J]. J Clin Oncol, 2016, 34(23):2784-2796.

[13] Pancreatic Cancer Committee of Chinese Anti-Cancer Association. Comprehensive guidelines for the diagnosis and treatment of pancreatic cancer(2018 version)[J]. J Clin Hepatol,2018, 34(10):2109-2120.(in Chinese）中国抗癌协会胰腺癌专业委员会．胰腺癌综合诊治指南（2018版）[J]．临床肝胆病杂志，2018, 34(10):2109-2120.

[14] TIERNEY JF, STEWART LA, GHERSI D, et al. Practical methods for incorporating summary time-to-event data into meta-analysis[J]. Trials, 2007, 8:16.

[15] MOORE MJ, GOLDSTEIN D, HAMM J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer:A phase III trial of the National Cancer Institute of Canada Clinical Trials Group[J]. J Clin Oncol, 2007, 25(15):1960-1966.

[16] CASCINU S, BERARDI R, LABIANCA R, et al. Cetuximab plus gemcitabine and cisplatin compared with gemcitabine and cisplatin alone in patients with advanced pancreatic cancer:A randomised, multicentre, phase II trial[J]. Lancet Oncol, 2008, 9(1):39-44.

[17] PHILIP PA, BENEDETTI J, CORLESS CL, et al. Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma:Southwest Oncology Group-directed intergroup trial S0205[J]. J Clin Oncol, 2010, 28(22):3605-3610.

[18] PROPPER D, DAVIDENKO I, BRIDGEWATER J, et al. Phase II, randomized, biomarker identification trial(MARK)for erlotinib in patients with advanced pancreatic carcinoma[J]. Ann Oncol, 2014, 25(7):1384-1390.

[19] WANG JP, WU CY, YEH YC, et al. Erlotinib is effective in pancreatic cancer with epidermal growth factor receptor mutations:A randomized, open-label, prospective trial[J]. Oncotarget,2015, 6(20):18162-18173.

[20] BURTNESS B, POWELL M, CATALANO P, et al. Randomized phaseⅡtrial of irinotecan/docetaxel or irinotecan/docetaxel plus cetuximab for metastatic pancreatic cancer:An Eastern Cooperative Oncology Group Study[J]. Am J Clin Oncol,2016, 39(4):340-345.

[21] HAMMEL P, HUGUET F, van LAETHEM JL, et al. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4months of gemcitabine with or without erlotinib:The LAP07randomized clinical trial[J]. JAMA, 2016, 315(17):1844-1853.

[22] SCHULTHEIS B, REUTER D, EBERT MP, et al. Gemcitabine combined with the monoclonal antibody nimotuzumab is an active first-line regimen in KRAS wildtype patients with locally advanced or metastatic pancreatic cancer:A multicenter, randomized phase IIb study[J]. Ann Oncol, 2017, 28(10):2429-2435.

[23] HARTWIG W, WERNER J, JÄGER D, et al. Improvement of surgical results for pancreatic cancer[J]. Lancet Oncol,2013, 14(11):e476-e485.

[24] JIN KZ, HUANG QY, LIU C, et al. New advances in diagnosis and treatment of pancreatic cancer[J]. Chin J Dig Surg,2019, 18(7):657-661.(in Chinese）金凯舟，黄秋依，刘辰，等．胰腺癌诊断与治疗的新进展[J]．中华消化外科杂志，2019, 18(7):657-661.

[25] GILLEN S, SCHUSTER T, MEYER ZUM BÜSCHENFELDE C,et al. Preoperative/neoadjuvant therapy in pancreatic cancer:A systematic review and meta-analysis of response and resection percentages[J]. PLoS Med, 2010, 7(4):e1000267.

[26] KAMISAWA T, ISAWA T, KOIKE M, et al. Hematogenous metastases of pancreatic ductal carcinoma[J]. Pancreas, 1995,11(4):345-349.

[27] KAMISAWA T, WOOD LD, ITOI T, et al. Pancreatic cancer[J]. Lancet, 2016, 388(10039):73-85.

[28] QIAN ZR, RUBINSON DA, NOWAK JA, et al. Association of alterations in main driver genes with outcomes of patients with resected pancreatic ductal adenocarcinoma[J]. JAMA Oncol, 2018, 4(3):e173420.

[29] KANDA M, MATTHAEI H, WU J, et al. Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia[J]. Gastroenterology, 2012, 142(4):730-733.

[30] ARDITO CM, GRÜNER BM, TAKEUCHI KK, et al. EGF receptor is required for KRAS-induced pancreatic tumorigenesis[J]. Cancer Cell, 2012, 22(3):304-317.

[31] HALFDANARSON TR, FOSTER NR, KIM GP, et al. A phaseⅡrandomized trial of panitumumab, erlotinib, and gemcitabine versus erlotinib and gemcitabine in patients with untreated, metastatic pancreatic adenocarcinoma:North Central Cancer Treatment Group Trial N064B(Alliance)[J]. Oncologist, 2019, 24(5):589-e160.

[32] MARON R, SCHECHTER B, NATARAJ NB, et al. Inhibition of a pancreatic cancer model by cooperative pairs of clinically approved and experimental antibodies[J]. Biochem Biophys Res Commun, 2019, 513(1):219-225.

[33] BLASCO MT, NAVAS C, MARTÍN-SERRANO G, et al. Complete regression of advanced pancreatic ductal adenocarcinomas upon combined inhibition of EGFR and C-RAF[J].Cancer Cell, 2019, 35(4):573-587.

[34] LI Z, WANG M, YAO X, et al. Development of a novel EGFRtargeting antibody-drug conjugate for pancreatic cancer therapy[J]. Target Oncol, 2019, 14(1):93-105.

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