Efficacy and safety of tyrosine kinase inhibitors in the treatment of HER2-positive breast cancer： a meta-analysis

XU Yinxue; SHEN Xiaolan; LU Xiufen; ZHANG Xuehui

doi:10.6039/j.issn.1001-0408.2024.03.17

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Efficacy and safety of tyrosine kinase inhibitors in the treatment of HER2-positive breast cancer： a meta-analysis

更新时间：2024-02-07

- Efficacy and safety of tyrosine kinase inhibitors in the treatment of HER2-positive breast cancer： a meta-analysis
- ZHONGGUO YAOFANG Vol. 35, Issue 3, Pages: 361-367(2024)
- 作者机构：
  
  南京医科大学附属江苏盛泽医院药学部，江苏苏州　215228
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.03.17
  CLC： R979.1
- Published：15 February 2024，
  
  Received：09 May 2023，
  
  Revised：24 October 2023，
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徐吟雪,沈晓岚,陆秀芬等.TKI类药物治疗HER2阳性乳腺癌的疗效与安全性的Meta分析 ^Δ[J].中国药房,2024,35(03):361-367.

XU Yinxue,SHEN Xiaolan,LU Xiufen,et al.Efficacy and safety of tyrosine kinase inhibitors in the treatment of HER2-positive breast cancer： a meta-analysis[J].ZHONGGUO YAOFANG,2024,35(03):361-367.
徐吟雪,沈晓岚,陆秀芬等.TKI类药物治疗HER2阳性乳腺癌的疗效与安全性的Meta分析 ^Δ[J].中国药房,2024,35(03):361-367. DOI： 10.6039/j.issn.1001-0408.2024.03.17.

XU Yinxue,SHEN Xiaolan,LU Xiufen,et al.Efficacy and safety of tyrosine kinase inhibitors in the treatment of HER2-positive breast cancer： a meta-analysis[J].ZHONGGUO YAOFANG,2024,35(03):361-367. DOI： 10.6039/j.issn.1001-0408.2024.03.17.

摘要

目的

评价酪氨酸激酶抑制剂（TKI）类药物治疗人表皮生长因子受体2（HER2）阳性乳腺癌的疗效和安全性，为临床用药提供循证学依据。

方法

计算机检索中国知网、万方数据库、维普网、PubMed、Cochrane Library、Embase、Web of Science数据库发表的关于TKI类药物（试验组）对比不含TKI类药物（对照组）的方案治疗HER2阳性乳腺癌的随机对照研究（RCT），检索年限为建库到2023年4月，使用RevMan 5.4.1和Stata 17软件进行Meta分析和敏感性分析。

结果

共纳入RCT 24篇，HER2阳性乳腺癌患者15 538例。Meta分析结果显示，与对照组相比，试验组的无进展生存期（PFS）[HR＝0.91，95%CI（0.80，1.02），

＝0.12]、总生存期（OS）[HR＝0.95，95%CI（0.89，1.01），

＝0.11]、客观缓解率（ORR）[OR＝1.21，95%CI（0.86，1.69），

＝0.27]和病理完全缓解率（pCR）[OR＝1.44，95%CI（0.91，2.27），

＝0.12]差异无统计学意义；在3/4级药品不良反应中，试验组患者发生贫血[OR＝1.77，95%CI（1.16，2.70），

＝0.008]、皮疹[OR＝11.26，95%CI（7.32，17.31），

＜0.000 01]、甲沟炎[OR＝8.67，95%CI（1.62，46.53），

＝0.01]、腹泻[OR＝10.17，95%CI（5.03，20.58），

＜0.000 01]、口腔黏膜炎[OR＝9.34，95%CI（3.13，27.83），

＜0.000 1]、天冬氨酸转氨酶升高[OR＝2.09，95%CI（1.13，3.84），

＝0.02]和低钾血症[OR＝2.37，95%CI（1.31，4.30），

＝0.005]的发生率显著高于对照组。亚组分析结果显示，与安慰剂组相比，TKI能提高OS、ORR（

＜0.05）；与曲妥珠单抗组相比，TKI在改善PFS、OS、ORR、pCR指标方面没有优势；而与曲妥珠单抗组相比，TKI联合曲妥珠单抗能显著提高患者的PFS、OS、ORR和pCR（

＜0.05）。敏感性分析提示结果较为稳健，发表偏倚风险较小。

结论

与曲妥珠单抗相比，TKI类药物治疗HER2阳性乳腺癌在改善PFS、OS、ORR、pCR方面没有优势，但TKI类药物和曲妥珠单抗联用能显著提高患者的PFS、OS、ORR、pCR；TKI类药物可增加3/4级贫血、皮疹、甲沟炎、腹泻、口腔黏膜炎、天冬氨酸转氨酶升高和低钾血症的风险。

Abstract

OBJECTIVE

To evaluate the efficacy and safety of tyrosine kinase inhibitors （TKI） in the treatment of HER2-positive breast cancer in order to provide evidence-based evidence for clinical medication.

METHODS

Retrieved from CNKI， Wanfang database， VIP， PubMed， Cochrane Library， Embase and Web of Science， randomized controlled trial （RCT） about TKI （trial group） versus drugs excluding TKI （control group） in the treatment of HER2-positive breast cancer were collected from the establishment of the database to April 2023. Meta-analysis and sensitivity analysis were performed by using RevMan 5.4.1 and Stata 17 software.

RESULTS

Total of 24 RCT studies were included， involving 15 538 HER2-positive breast cancer patients. The meta-analysis results showed that compared with the control group， the progression-free survival （PFS） [HR＝0.91， 95%CI （0.80， 1.02），

＝0.12]， overall survival （OS） [HR＝0.95， 95%CI （0.89， 1.01），

＝0.11]， objective response rate （ORR） [OR＝1.21， 95%CI （0.86， 1.69），

＝0.27]， and pathological complete response rate （pCR） [OR＝1.44， 95%CI （0.91， 2.27），

＝0.12] had no statistically significant difference in the trial group； among the 3/4 grade ADRs， the trial group had a higher incidence of anemia [OR＝1.77， 95%CI （1.16，2.70），

＝0.008]， rash [OR＝11.26， 95%CI （7.32，17.31），

＜0.000 01]， paronychia [OR＝8.67， 95%CI（1.62，46.53），

＝0.01]， diarrhea [OR＝10.17， 95%CI（5.03，20.58），

＜0.000 01]， oral mucositis inflammation [OR＝9.34， 95%CI （3.13， 27.83），

＜0.000 1]， elevated aspartate aminotransferase [OR＝2.09， 95%CI （1.13，3.84），

＝0.02]， and hypokalemia [OR＝2.37， 95%CI （1.31，4.30），

＝0.005] than that of the control group. Subgroup analysis results showed that compared with the placebo group， TKI could improve OS and ORR （

＜0.05）， while compared with trastuzumab， TKI had no advantage in PFS， OS， ORR， and pCR， and TKI combined with trastuzumab could significantly improve PFS， OS， ORR， and pCR compared with the trastuzumab group （

＜0.05）. Sensitivity analysis suggested that the results were relatively robust and the risk of publication bias was low.

CONCLUSIONS

Compared with trastuzumab， TKI has no advantages in PFS， OS， ORR and pCR in the treatment of HER2-positive breast cancer， but TKI combined with trastuzumab can significantly improve PFS， OS， ORR and pCR； TKI can increase the risk of grade 3/4 anemia， rash， paronychia， diarrhea， oral mucositis， elevated aspartate aminotransferase， and hypokalemia.

关键词

酪氨酸激酶抑制剂人表皮生长因子受体2阳性乳腺癌疗效安全性

Keywords

HER2-positive breast cancerefficacysafety

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