Trastuzumab combined with chemotherapy for Her-2 positive patients with advanced gastric cancer: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

LI Long , ZHAN Hao , LONG Bo , ZHOU Huinian , ZHANG Gengyuan ,  JIAO Zuoyi

Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730030, P.R.China;

Corresponding author：

JIAO Zuoyi, Email: jiaozx@lzu.edu.cn

Keywords：

Advanced gastric cancer; Trastuzumab; Targeted therapy; Meta-analysis; Systematic review

DOI：

10.7507/1672-2531.201606021

Video：

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Objective To systematically evaluate the safety and efficacy of trastuzumab combined with chemotherapy for HER-2 positive patients with advanced gastric cancer. Methods We searched ClinicalTrails.gov, PubMed, EMbase, Web of Science, The Cochrane Library (Issue 5, 2016), CNKI, CBM, WanFang Data, VIP and major meeting proceeding databases (ASCO and ESMO) from inception to May 2016, to collect randomized controlled trials (RCTs) or non-RCTs about trastuzumab combined with chemotherapy versus chemotherapy alone for advanced gastric cancer. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was performed by using RevMan 5.3 software. Results Nine studies involving 1 034 HER-2 positive patients were included, of which three were RCTs and the other six were non-RCTs. Meta-analysis results indicated that the trastuzumab combined with chemotherapy group (the trial group) was superior to the chemotherapy alone group (the control group) in complete remission (OR=2.76, 95%CI 1.40 to 5.44,P=0.003), partial remission (OR=1.81, 95%CI 1.40 to 2.33,P<0.000 01), overall response rate (OR=2.09, 95%CI 1.63 to 2.68,P<0.000 01) and disease control rate (OR=2.20, 95%CI 1.63 to 2.98,P<0.000 1), while there was no statistical significances in stable disease (OR=0.87, 95%CI 0.66 to 1.14,P=0.31). In terms of safety, the incidence of diarrhea (OR=1.51, 95%CI 1.10 to 2.06,P=0.01) and erythra (OR=4.35, 95%CI 1.25 to 15.10,P=0.02) in the trial group were higher than the control group. However, other adverse reactions were no significant differences in two groups. Conclusion Compared with chemotherapy alone, trastuzumab combined with chemotherapy in the treatment of HER-2 positive patients with advanced gastric cancer can significantly improve response rate, but it may increase the incidence of diarrhea and erythra. Because of the limited quality and quantity of the included studies, the above conclusion needs to be verified by conducting more high quality studies.

Citation： LI Long, ZHAN Hao, LONG Bo, ZHOU Huinian, ZHANG Gengyuan, JIAO Zuoyi. Trastuzumab combined with chemotherapy for Her-2 positive patients with advanced gastric cancer: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2017, 17(1): 40-46. doi: 10.7507/1672-2531.201606021 Copy

1.	陈万青, 郑荣寿, 张思维, 等. 2012年中国恶性肿瘤发病和死亡分析. 中国肿瘤, 2016, 25(1): 1-8.
2.	季加孚. 我国胃癌防治研究三十年回顾. 中国肿瘤临床, 2013, 40(22): 1345-1351.
3.	Gomez-Martin C, Garralda E, Echarri MJ, et al. HER2/neu testing for anti-HER2-based therapies in patients with unresectable and/or metastatic gastric cancer. J Clin Pathol, 2012, 65(8): 751-757.
4.	Uprak TK, Attaallah W, Celikel CA, et al. HER-2 incidence in gastric cancer, its association with prognosis and clinicopathological parameters. Ulus Cerrahi Derg, 2015, 31(4): 207-213.
5.	Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet, 2010, 376(9742): 687-697.
6.	刘建平. 非随机研究的系统评价方法(一). 中国循证医学, 2001, 1(4): 239-243.
7.	张俊, 徐志伟, 李克. 诊断性试验Meta分析的效应指标评价. 中国循证医学杂志, 2013, 13(7): 890-895.
8.	孙杰, 潘赛英, 陈倩琪, 等. 曲妥珠单抗联合 FOLFIRI 治疗 HER2 阳性晚期胃癌的疗效观察. 南方医科大学学报, 2011, 31(8): 1458-1460.
9.	赵鹏, 陈炳光, 莫如康, 等. 曲妥珠单抗联合卡培他滨和顺铂治疗 HER-2 阳性晚期胃癌的应用. 国际医药卫生导报, 2012, 18(22): 3312-3315.
10.	饶志高, 王锡恩, 王幼辉, 等. 曲妥珠单抗联合卡培他滨及奥沙利铂治疗晚期胃癌疗效研究. 浙江医学, 2013, 35(21): 1906-1907, 1910.
11.	朱丽波, 马锐, 李琳琳, 等. 曲妥珠单抗联合奥沙利铂、5-氟尿嘧啶治疗 HER-2/neu 高表达晚期胃癌的临床疗效观察. 疑难病杂志, 2013, 12(12): 930-932.
12.	Qiu MZ, Li Q, Wang ZQ, et al. HER2-positive patients receiving trastuzumab treatment have a comparable prognosis with HER2-negative advanced gastric cancer patients: a prospective cohort observation. Int J Cancer, 2014, 134(10): 2468-2477.
13.	陈红宙, 庞林荣, 陈俊. 曲妥珠单抗联合 SOX 方案治疗晚期胃癌临床研究. 现代实用医学, 2015, 27(3): 335-337.
14.	李祥, 蓝晓红, 许锐, 等. 曲妥珠单抗联合卡培他滨和顺铂治疗晚期胃癌疗效观察. 人民军医, 2015, 58(5): 539-541.
15.	杨雅雯, 郑继成, 陈飞, 等. 曲妥珠单抗联合 SOX 方案对晚期胃癌的治疗效果探讨. 中国继续医学教育, 2015, 7(30): 148-149.
16.	王萍, 谢蟪旭, 张绮, 等. 如何在 Cochrane 系统评价中设计资料提取表. 中国循证医学杂志, 2011, 7(3): 341-345.
17.	Gu J, Zheng L, Wang Y, et al. Prognostic significance of HER2 expression based on trastuzumab for gastric cancer (ToGA) criteria in gastric cancer: an updated meta-analysis. Tumour Biol, 2014, 35(6): 5315-5321.
18.	Nagaraja V, Eslick GD. HER2 expression in gastric and oesophageal cancer: a meta-analytic review. J Gastrointest Oncol, 2015, 6(2): 143-154.
19.	Kucukoner M, Isikdogan A, Arpaci E, et al. Adjuvant chemoradiation for gastric cancer: multicentric study of the Anatolian Society of Medical Oncology. Hepatogastroenterology, 2012, 59(119): 2343-2347.
20.	Waddell T, Chau I, Cunningham D, et al. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol, 2013, 14(6): 481-489.
21.	张秀宝, 项荣武, 赵庆春, 等. 西妥昔单抗疗效与皮疹相关性的系统评价. 中国循证医学杂志, 2015, 15(2): 181-187.
22.	Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med, 2005, 353(16): 1673-1684.
23.	Hahn VS, Lenihan DJ, Ky B. Cancer therapy-induced cardiotoxicity: basic mechanisms and potential cardioprotective therapies. J Am Heart Assoc, 2014, 3(2): e000665.
24.	Curigliano G, Cardinale D, Dent S, et al. Cardiotoxicity of anticancer treatments: Epidemiology, detection, and management. CA Cancer J Clin, 2016, 66(4): 309-325.
25.	Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, et al. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet, 2013, 382(9897): 1021-1028.
26.	刘永军, 马林超. 曲妥珠单抗辅助化疗治疗 HER2 阳性乳腺癌有效性和安全性的 Meta 分析. 中国药物评价, 2015, 32(1): 35-40.
27.	戎佩佩. 曲妥珠单抗联合化疗用于 Her-2 阳性晚期胃癌的成本-效果分析. 中国药房, 2015, 26(5): 577-579.
28.	孙薇薇, 陈文. 曲妥珠单抗治疗转移性胃癌的临床效果和经济学结果. 中国药房, 2015, 26(23): 3309-3312.
29.	Network NCC. NCCN clinical practice guidelines in oncology (NCCN guidelines): gastric cancer. 3 ed. 2016.
30.	李幼平, 李静, 孙鑫, 等. 循证医学在中国的起源与发展: 献给中国循证医学 20 周年. 中国循证医学杂志, 2016, 16(1): 2-6.
31.	杨洁, 武赞凯, 李连顺, 等. 胃癌 Lauren 分型研究进展. 中南大学学报(医学版), 2015, 40(8): 934-940.
32.	Cunningham D, Starling N, Rao S, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med, 2008, 358(1): 36-46.
33.	Shitara K, Yatabe Y, Matsuo K, et al. Prognosis of patients with advanced gastric cancer by HER2 status and trastuzumab treatment. Gastric Cancer, 2013, 16(2): 261-267.

1. 陈万青, 郑荣寿, 张思维, 等. 2012年中国恶性肿瘤发病和死亡分析. 中国肿瘤, 2016, 25(1): 1-8.
2. 季加孚. 我国胃癌防治研究三十年回顾. 中国肿瘤临床, 2013, 40(22): 1345-1351.
3. Gomez-Martin C, Garralda E, Echarri MJ, et al. HER2/neu testing for anti-HER2-based therapies in patients with unresectable and/or metastatic gastric cancer. J Clin Pathol, 2012, 65(8): 751-757.
4. Uprak TK, Attaallah W, Celikel CA, et al. HER-2 incidence in gastric cancer, its association with prognosis and clinicopathological parameters. Ulus Cerrahi Derg, 2015, 31(4): 207-213.
5. Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet, 2010, 376(9742): 687-697.
6. 刘建平. 非随机研究的系统评价方法(一). 中国循证医学, 2001, 1(4): 239-243.
7. 张俊, 徐志伟, 李克. 诊断性试验Meta分析的效应指标评价. 中国循证医学杂志, 2013, 13(7): 890-895.
8. 孙杰, 潘赛英, 陈倩琪, 等. 曲妥珠单抗联合 FOLFIRI 治疗 HER2 阳性晚期胃癌的疗效观察. 南方医科大学学报, 2011, 31(8): 1458-1460.
9. 赵鹏, 陈炳光, 莫如康, 等. 曲妥珠单抗联合卡培他滨和顺铂治疗 HER-2 阳性晚期胃癌的应用. 国际医药卫生导报, 2012, 18(22): 3312-3315.
10. 饶志高, 王锡恩, 王幼辉, 等. 曲妥珠单抗联合卡培他滨及奥沙利铂治疗晚期胃癌疗效研究. 浙江医学, 2013, 35(21): 1906-1907, 1910.
11. 朱丽波, 马锐, 李琳琳, 等. 曲妥珠单抗联合奥沙利铂、5-氟尿嘧啶治疗 HER-2/neu 高表达晚期胃癌的临床疗效观察. 疑难病杂志, 2013, 12(12): 930-932.
12. Qiu MZ, Li Q, Wang ZQ, et al. HER2-positive patients receiving trastuzumab treatment have a comparable prognosis with HER2-negative advanced gastric cancer patients: a prospective cohort observation. Int J Cancer, 2014, 134(10): 2468-2477.
13. 陈红宙, 庞林荣, 陈俊. 曲妥珠单抗联合 SOX 方案治疗晚期胃癌临床研究. 现代实用医学, 2015, 27(3): 335-337.
14. 李祥, 蓝晓红, 许锐, 等. 曲妥珠单抗联合卡培他滨和顺铂治疗晚期胃癌疗效观察. 人民军医, 2015, 58(5): 539-541.
15. 杨雅雯, 郑继成, 陈飞, 等. 曲妥珠单抗联合 SOX 方案对晚期胃癌的治疗效果探讨. 中国继续医学教育, 2015, 7(30): 148-149.
16. 王萍, 谢蟪旭, 张绮, 等. 如何在 Cochrane 系统评价中设计资料提取表. 中国循证医学杂志, 2011, 7(3): 341-345.
17. Gu J, Zheng L, Wang Y, et al. Prognostic significance of HER2 expression based on trastuzumab for gastric cancer (ToGA) criteria in gastric cancer: an updated meta-analysis. Tumour Biol, 2014, 35(6): 5315-5321.
18. Nagaraja V, Eslick GD. HER2 expression in gastric and oesophageal cancer: a meta-analytic review. J Gastrointest Oncol, 2015, 6(2): 143-154.
19. Kucukoner M, Isikdogan A, Arpaci E, et al. Adjuvant chemoradiation for gastric cancer: multicentric study of the Anatolian Society of Medical Oncology. Hepatogastroenterology, 2012, 59(119): 2343-2347.
20. Waddell T, Chau I, Cunningham D, et al. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol, 2013, 14(6): 481-489.
21. 张秀宝, 项荣武, 赵庆春, 等. 西妥昔单抗疗效与皮疹相关性的系统评价. 中国循证医学杂志, 2015, 15(2): 181-187.
22. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med, 2005, 353(16): 1673-1684.
23. Hahn VS, Lenihan DJ, Ky B. Cancer therapy-induced cardiotoxicity: basic mechanisms and potential cardioprotective therapies. J Am Heart Assoc, 2014, 3(2): e000665.
24. Curigliano G, Cardinale D, Dent S, et al. Cardiotoxicity of anticancer treatments: Epidemiology, detection, and management. CA Cancer J Clin, 2016, 66(4): 309-325.
25. Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, et al. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet, 2013, 382(9897): 1021-1028.
26. 刘永军, 马林超. 曲妥珠单抗辅助化疗治疗 HER2 阳性乳腺癌有效性和安全性的 Meta 分析. 中国药物评价, 2015, 32(1): 35-40.
27. 戎佩佩. 曲妥珠单抗联合化疗用于 Her-2 阳性晚期胃癌的成本-效果分析. 中国药房, 2015, 26(5): 577-579.
28. 孙薇薇, 陈文. 曲妥珠单抗治疗转移性胃癌的临床效果和经济学结果. 中国药房, 2015, 26(23): 3309-3312.
29. Network NCC. NCCN clinical practice guidelines in oncology (NCCN guidelines): gastric cancer. 3 ed. 2016.
30. 李幼平, 李静, 孙鑫, 等. 循证医学在中国的起源与发展: 献给中国循证医学 20 周年. 中国循证医学杂志, 2016, 16(1): 2-6.
31. 杨洁, 武赞凯, 李连顺, 等. 胃癌 Lauren 分型研究进展. 中南大学学报(医学版), 2015, 40(8): 934-940.
32. Cunningham D, Starling N, Rao S, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med, 2008, 358(1): 36-46.
33. Shitara K, Yatabe Y, Matsuo K, et al. Prognosis of patients with advanced gastric cancer by HER2 status and trastuzumab treatment. Gastric Cancer, 2013, 16(2): 261-267.

Chinese Journal of Evidence-Based Medicine

Trastuzumab combined with chemotherapy for Her-2 positive patients with advanced gastric cancer: a meta-analysis

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