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

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.

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