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.	陳萬青, 鄭榮壽, 張思維, 等. 2012年中國惡性腫瘤發病和死亡分析. 中國腫瘤, 2016, 25(1): 1-8.
2.	季加孚. 我國胃癌防治研究三十年回顧. 中國腫瘤臨床, 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.	劉建平. 非隨機研究的系統評價方法(一). 中國循證醫學, 2001, 1(4): 239-243.
7.	張俊, 徐志偉, 李克. 診斷性試驗Meta分析的效應指標評價. 中國循證醫學雜志, 2013, 13(7): 890-895.
8.	孫杰, 潘賽英, 陳倩琪, 等. 曲妥珠單抗聯合 FOLFIRI 治療 HER2 陽性晚期胃癌的療效觀察. 南方醫科大學學報, 2011, 31(8): 1458-1460.
9.	趙鵬, 陳炳光, 莫如康, 等. 曲妥珠單抗聯合卡培他濱和順鉑治療 HER-2 陽性晚期胃癌的應用. 國際醫藥衛生導報, 2012, 18(22): 3312-3315.
10.	饒志高, 王錫恩, 王幼輝, 等. 曲妥珠單抗聯合卡培他濱及奧沙利鉑治療晚期胃癌療效研究. 浙江醫學, 2013, 35(21): 1906-1907, 1910.
11.	朱麗波, 馬銳, 李琳琳, 等. 曲妥珠單抗聯合奧沙利鉑、5-氟尿嘧啶治療 HER-2/neu 高表達晚期胃癌的臨床療效觀察. 疑難病雜志, 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.	陳紅宙, 龐林榮, 陳俊. 曲妥珠單抗聯合 SOX 方案治療晚期胃癌臨床研究. 現代實用醫學, 2015, 27(3): 335-337.
14.	李祥, 藍曉紅, 許銳, 等. 曲妥珠單抗聯合卡培他濱和順鉑治療晚期胃癌療效觀察. 人民軍醫, 2015, 58(5): 539-541.
15.	楊雅雯, 鄭繼成, 陳飛, 等. 曲妥珠單抗聯合 SOX 方案對晚期胃癌的治療效果探討. 中國繼續醫學教育, 2015, 7(30): 148-149.
16.	王萍, 謝蟪旭, 張綺, 等. 如何在 Cochrane 系統評價中設計資料提取表. 中國循證醫學雜志, 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.	張秀寶, 項榮武, 趙慶春, 等. 西妥昔單抗療效與皮疹相關性的系統評價. 中國循證醫學雜志, 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.	劉永軍, 馬林超. 曲妥珠單抗輔助化療治療 HER2 陽性乳腺癌有效性和安全性的 Meta 分析. 中國藥物評價, 2015, 32(1): 35-40.
27.	戎佩佩. 曲妥珠單抗聯合化療用于 Her-2 陽性晚期胃癌的成本-效果分析. 中國藥房, 2015, 26(5): 577-579.
28.	孫薇薇, 陳文. 曲妥珠單抗治療轉移性胃癌的臨床效果和經濟學結果. 中國藥房, 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, 李靜, 孫鑫, 等. 循證醫學在中國的起源與發展: 獻給中國循證醫學 20 周年. 中國循證醫學雜志, 2016, 16(1): 2-6.
31.	楊潔, 武贊凱, 李連順, 等. 胃癌 Lauren 分型研究進展. 中南大學學報(醫學版), 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. 陳萬青, 鄭榮壽, 張思維, 等. 2012年中國惡性腫瘤發病和死亡分析. 中國腫瘤, 2016, 25(1): 1-8.
2. 季加孚. 我國胃癌防治研究三十年回顧. 中國腫瘤臨床, 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. 劉建平. 非隨機研究的系統評價方法(一). 中國循證醫學, 2001, 1(4): 239-243.
7. 張俊, 徐志偉, 李克. 診斷性試驗Meta分析的效應指標評價. 中國循證醫學雜志, 2013, 13(7): 890-895.
8. 孫杰, 潘賽英, 陳倩琪, 等. 曲妥珠單抗聯合 FOLFIRI 治療 HER2 陽性晚期胃癌的療效觀察. 南方醫科大學學報, 2011, 31(8): 1458-1460.
9. 趙鵬, 陳炳光, 莫如康, 等. 曲妥珠單抗聯合卡培他濱和順鉑治療 HER-2 陽性晚期胃癌的應用. 國際醫藥衛生導報, 2012, 18(22): 3312-3315.
10. 饒志高, 王錫恩, 王幼輝, 等. 曲妥珠單抗聯合卡培他濱及奧沙利鉑治療晚期胃癌療效研究. 浙江醫學, 2013, 35(21): 1906-1907, 1910.
11. 朱麗波, 馬銳, 李琳琳, 等. 曲妥珠單抗聯合奧沙利鉑、5-氟尿嘧啶治療 HER-2/neu 高表達晚期胃癌的臨床療效觀察. 疑難病雜志, 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. 陳紅宙, 龐林榮, 陳俊. 曲妥珠單抗聯合 SOX 方案治療晚期胃癌臨床研究. 現代實用醫學, 2015, 27(3): 335-337.
14. 李祥, 藍曉紅, 許銳, 等. 曲妥珠單抗聯合卡培他濱和順鉑治療晚期胃癌療效觀察. 人民軍醫, 2015, 58(5): 539-541.
15. 楊雅雯, 鄭繼成, 陳飛, 等. 曲妥珠單抗聯合 SOX 方案對晚期胃癌的治療效果探討. 中國繼續醫學教育, 2015, 7(30): 148-149.
16. 王萍, 謝蟪旭, 張綺, 等. 如何在 Cochrane 系統評價中設計資料提取表. 中國循證醫學雜志, 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. 張秀寶, 項榮武, 趙慶春, 等. 西妥昔單抗療效與皮疹相關性的系統評價. 中國循證醫學雜志, 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. 劉永軍, 馬林超. 曲妥珠單抗輔助化療治療 HER2 陽性乳腺癌有效性和安全性的 Meta 分析. 中國藥物評價, 2015, 32(1): 35-40.
27. 戎佩佩. 曲妥珠單抗聯合化療用于 Her-2 陽性晚期胃癌的成本-效果分析. 中國藥房, 2015, 26(5): 577-579.
28. 孫薇薇, 陳文. 曲妥珠單抗治療轉移性胃癌的臨床效果和經濟學結果. 中國藥房, 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, 李靜, 孫鑫, 等. 循證醫學在中國的起源與發展: 獻給中國循證醫學 20 周年. 中國循證醫學雜志, 2016, 16(1): 2-6.
31. 楊潔, 武贊凱, 李連順, 等. 胃癌 Lauren 分型研究進展. 中南大學學報(醫學版), 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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