Efficacy and safety of trastuzumab with or without a tyrosine kinase inhibitor for HER2-positive breast cancer: A systematic review and meta-analysis

Biochim Biophys Acta Rev Cancer. 2023 Nov;1878(6):188969. doi: 10.1016/j.bbcan.2023.188969. Epub 2023 Aug 26.

Abstract

Background: This study aimed to explore the efficacy and safety of trastuzumab plus tyrosine kinase inhibitors (TKIs) compared with those of trastuzumab monotherapy in patients with human epidermal growth factor receptor (HER2)-positive breast cancer.

Methods: The PubMed, Embase, Cochrane, and Web of Science databases were systematically searched for relevant articles from inception until September 2022. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Subgroup analyses were performed based on disease status, TKI type, and hormone receptor status.

Results: Sixteen studies were included in the current analysis. Trastuzumab plus TKI significantly improved OS and PFS compared to trastuzumab monotherapy. In the neoadjuvant setting, trastuzumab plus TKI significantly increased the pathologic complete response (pCR) rate compared to trastuzumab monotherapy. Moreover, a higher objective response rate (ORR) was observed with trastuzumab plus TKI. Patients who received the combination therapy had a higher incidence of discontinuation, all-grade diarrhea, and grade ≥ 3 diarrhea.

Conclusions: Trastuzumab plus TKI was better than trastuzumab monotherapy for treating different stages of HER2-positive breast cancer. The safety of trastuzumab plus TKI anti-HER2 therapy was controllable. The different efficacies of TKIs combined with trastuzumab may be related to the mechanism of action of the different TKIs, needing further investigations.

Keywords: Breast cancer; Human epidermal growth factor receptor-positive; Targeted therapy; Trastuzumab; Tyrosine kinase inhibitor.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Diarrhea / chemically induced
  • Female
  • Humans
  • Protein Kinase Inhibitors / adverse effects
  • Receptor, ErbB-2 / metabolism
  • Trastuzumab / adverse effects
  • Tyrosine Kinase Inhibitors

Substances

  • Trastuzumab
  • Tyrosine Kinase Inhibitors
  • Receptor, ErbB-2
  • Protein Kinase Inhibitors