title: Efficacy and safety of lapatinib and trastuzumab for HER2-positive breast cancer: a systematic review and meta-analysis of randomised controlled trials.
abstract: The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour actively in models of HER2-positive breast cancer. However, the efficacy of trastuzumab in combination with lapatinib remains controversial. Therefore, we conducted this meta-analysis to compare combination treatment with lapatinib and trastuzumab to trastuzumab or lapatinib alone in the treatment of HER2-positive breast cancer.
  
  
  
  Randomised controlled trials (RCTs), published in PubMed, Embase and Web of Science, were systematically reviewed to assess the survival benefits and toxicity profile of HER2-positive patients with breast cancer who were treated with lapatinib and trastuzumab. Outcomes included pathological complete response (pCR), event-free survival (EFS), overall survival (OS) and toxicities. Results were expressed as the risk ratio (RR) or HR with 95% CIs. Pooled estimates were calculated by using a fixed-effects model or a randomised-effects model.
  
  
  
  A total of 7 RCTs involving 2084 patients met the inclusion criteria and were included in this meta-analysis. The combination of lapatinib and trastuzumab significantly improved pCR (RR=1.43, 95% CI 1.23 to 1.67; p<0.001), EFS (HR=0.75, 95% CI 0.60 to 0.93; p=0.009) and OS (HR=0.72, 95% CI 0.56 to 0.93; p=0.011) in the treatment of HER2-positive breast cancer compared with trastuzumab or lapatinib alone. The combination treatment also increased the pCR irrespective of hormone receptor status and tumour size. More frequent grade 3 or 4 adverse events, including diarrhoea, rash or erythema, neutropenia and hepatic adverse events, were found in the combination group than in the trastuzumab or lapatinib group.
  
  
  
  On the basis of the current evidence, our results reveal that the addition of lapatinib to trastuzumab can significantly improve pCR, EFS and OS with a tolerated toxicity in patients with HER2-positive breast cancer. Further well-conducted, large-scale trials are needed to validate these findings.
authors.affiliation: Tumor Center, Kaifeng Central Hospital, Kaifeng, China.
authors.forename: Zhi-Qiao
authors.initials: ZQ
authors.lastname: Xu
authors.affiliation: Tumor Center, Kaifeng Central Hospital, Kaifeng, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Tumor Center, Kaifeng Central Hospital, Kaifeng, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Tumor Center, Kaifeng Central Hospital, Kaifeng, China.
authors.forename: Pei-Jie
authors.initials: PJ
authors.lastname: Liu
authors.affiliation: Tumor Center, Kaifeng Central Hospital, Kaifeng, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.affiliation: Tumor Center, Kaifeng Central Hospital, Kaifeng, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.affiliation: Tumor Center, Kaifeng Central Hospital, Kaifeng, China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Tie
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D000068878:Trastuzumab / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D000074322:Antineoplastic Agents, Immunological; D000077341:Lapatinib; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: HER2-positive; breast cancer; lapatinib; meta-analysis; trastuzumab