Lapatinib and lapatinib plus trastuzumab therapy versus trastuzumab therapy for HER2 positive breast cancer patients: an updated systematic review and meta-analysis

Syst Rev. 2022 Dec 10;11(1):264. doi: 10.1186/s13643-022-02134-9.

Abstract

Introduction: Trastuzumab, as the gold standard for HER2-positive BC treatment, was the first-line HER2 targeted drug. However, some studies reported patients benefited more from lapatinib and lapatinib plus trastuzumab therapy than standard trastuzumab therapy. This study presents an update of a systematic review and meta-analysis involving comparison of lapatinib and lapatinib plus trastuzumab therapy versus trastuzumab therapy.

Aim: We determined whether trastuzumab plus lapatinib or lapatinib therapy is not inferior to trastuzumab therapy in HER2-positive breast cancer patients.

Methods: Relevant trials were searched in CNKI, Wanfang, VIP, Sinomed, PubMed, Embase, and Cochrane CENTRAL databases from inception until October 25, 2021. Primary outcomes were OS, DFS/EFS, and PFS while secondary outcomes were pCR (ypT0/is ypN0), pCR (ypT0/is ypN0/+), ORR, DCR, rate of BCS, RFS, cardiac toxicities, and other toxicities.

Results: Thirteen randomized controlled trials were included in this study. Trastuzumab combined with lapatinib therapy was found to be superior to standard trastuzumab therapy alone with regard to overall survival, disease-free survival/event-free survival, pathologic complete response (ypT0/is ypN0), pathologic complete response (ypT0/is ypN0/+), recurrence-free survival, higher incidences of diarrhea, and rash/skin toxicity. Lapatinib therapy was established to be inferior to trastuzumab therapy in overall survival, progression-free survival, disease-free survival/event-free survival, pathologic complete response (ypT0/is ypN0) and pathologic complete response (ypT0/is ypN0/+), diarrhea, and rash/skin toxicity and had a low incidence of left ventricular ejection fraction decline.

Conclusions: The efficacy of trastuzumab combined with lapatinib therapy is superior to standard trastuzumab therapy alone; however, it has more non-cardiac grade III/IV toxicities. Moreover, the efficacy of lapatinib therapy is inferior to that of standard trastuzumab therapy alone.

Keywords: Breast cancer; HER2 positive; Lapatinib; Meta-analysis; Randomized controlled trials; Systematic review; Trastuzumab.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms*
  • Female
  • Humans
  • Lapatinib / therapeutic use
  • Randomized Controlled Trials as Topic
  • Receptor, ErbB-2
  • Stroke Volume
  • Trastuzumab / adverse effects
  • Ventricular Function, Left

Substances

  • Trastuzumab
  • Lapatinib
  • Receptor, ErbB-2