title: Efficacy and Safety of HER2-Targeted Agents for Breast Cancer with HER2-Overexpression: A Network Meta-Analysis.
abstract: BACKGROUND
  Clinical trials of human epidermal growth factor receptor 2 (HER2)-targeted agents added to standard treatment have been efficacious for HER2-positive (HER2+) advanced breast cancer. To our knowledge, no meta-analysis has evaluated HER2-targeted therapy including trastuzumab emtansine (T-DM1) and pertuzumab for HER2-positive breast caner and ranked the targeted treatments. We performed a network meta-analysis of both direct and indirect comparisons to evaluate the effect of adding HER2-targeted agents to standard treatment and examined side effects.
  
  
  METHODS
  We performed a Bayesian-framework network meta-analysis of randomized controlled trials to compare 6 HER2-targeted treatment regimens and 1 naïve standard treatment (NST, without any-targeted drugs) in targeted treatment of HER2+ breast cancer in adults. These treatment regimens were T-DM1, LC (lapatinib), HC (trastuzumab), PEC (pertuzumab), LHC (lapatinib and trastuzumab), and PEHC (pertuzumab and trastuzumab). The main outcomes were overall survival and response rates. We also examined side effects of rash, LVEF (left ventricular ejection fraction), fatigue, and gastrointestinal disorders, and performed subgroup analysis for the different treatment regimens in metastatic or advanced breast cancer.
  
  
  RESULTS
  We identified 25 articles of 21 trials, with data for 11,276 participants. T-DM1 and PEHC were more efficient drug regimens with regard to overall survival as compared with LHC, LC, HC and PEC. The incidence of treatment-related rash occurs more frequently in the patients who received LC treatment regimen than PEHC and T-DM1 and HC. In subgroup analysis, T-DM1 was associated with increased overall survival as compared with LC and HC. PEHC was associated with increased overall response as compared with LC, HC, and NST.
  
  
  CONCLUSIONS
  Overall, the regimen of T-DM1 as well as pertuzumab in combination with trastuzumab and docetaxel is efficacious with fewer side effects as compared with other regimens, especially for advanced HER2+ breast cancer.
  
  
  CONCLUSIONS
  This study suggests that both T-DM1 and PEHC therapy are potentially and equally useful treatments for HER2+ breast cancer.
authors.affiliation: Department of Public Health, Shantou University Medical College, No.22 Xinling Road, Shantou, Guangdong 515041, China.
authors.forename: Qiuyan
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Public Health, Shantou University Medical College, No.22 Xinling Road, Shantou, Guangdong 515041, China.
authors.forename: Zhenli
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Public Health, Shantou University Medical College, No.22 Xinling Road, Shantou, Guangdong 515041, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Public Health, Shantou University Medical College, No.22 Xinling Road, Shantou, Guangdong 515041, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Public Health, Shantou University Medical College, No.22 Xinling Road, Shantou, Guangdong 515041, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human