One year versus a shorter duration of adjuvant trastuzumab for HER2-positive early breast cancer: a systematic review and meta-analysis

Breast Cancer Res Treat. 2019 Jan;173(2):247-254. doi: 10.1007/s10549-018-5001-x. Epub 2018 Oct 13.

Abstract

Introduction: One year is the standard duration of adjuvant trastuzumab for human epidermal receptor-2 (HER2) positive (HER2+) breast cancer (BC). Indeed, a shorter duration of trastuzumab can reduce cardiotoxicity and the costs involved and could provide the same benefit as a one-year treatment. We evaluated the available evidence from randomised controlled trials (RCTs) by comparing 1 year versus a shorter duration of adjuvant trastuzumab for HER2+ BC.

Patients and methods: A systematic search of PubMed, EMBASE, The Cochrane Library and conference proceedings was carried out in order to identify the RCTs that investigated a standard versus a shorter duration of adjuvant trastuzumab in HER2+ BC patients. Using the fixed and random effects models, the pooled hazard ratios (HRs) and risk ratio (RR) with 95% confidence intervals (CI) were calculated for overall survival (OS), disease-free survival (DFS) and cardiac events.

Results: Five RCTs with a total of 11,381 patients were included. Overall, one year of adjuvant trastuzumab improved OS (HR 1.22, 95% CI 1.07-1.39; P = 0.003) and DFS (HR 1.19, 95% CI 1.08-1.3; P < 0.001) compared with a shorter duration (6 months and 9 weeks). In the subgroup analysis, there was a trend towards better DFS with the 1-year duration for patients with high-risk features, and also for concomitant administration of chemotherapy and trastuzumab. Cardiac events were significantly lower with a shorter duration (RR 0.4, 95% CI 0.32-0.49; P < 0.001).

Conclusions: One-year adjuvant trastuzumab is associated with better DFS and OS compared with shorter durations and should still be considered the standard duration. However, selected patients with low-risk HER2+ BC can most likely be spared from an excess of cardiac toxicity with a shorter course.

Keywords: Adjuvant; Breast cancer; Duration; One year; Trastuzumab.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antineoplastic Agents, Immunological / administration & dosage*
  • Antineoplastic Agents, Immunological / adverse effects
  • Breast / surgery
  • Breast Neoplasms / immunology
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Cardiotoxicity / etiology
  • Cardiotoxicity / prevention & control*
  • Chemotherapy, Adjuvant / adverse effects
  • Chemotherapy, Adjuvant / methods
  • Disease-Free Survival
  • Female
  • Humans
  • Mastectomy
  • Randomized Controlled Trials as Topic
  • Receptor, ErbB-2 / metabolism
  • Time Factors
  • Trastuzumab / administration & dosage*
  • Trastuzumab / adverse effects

Substances

  • Antineoplastic Agents, Immunological
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab