Optimal duration of adjuvant trastuzumab in treatment of early breast cancer: a meta-analysis of randomized controlled trials

Abstract

Background: One year of adjuvant trastuzumab, chosen empirically, improves survival of women with early-stage, Human Epidermal Growth Factor Receptor 2 (HER2) positive breast cancer. Two years of trastuzumab does not improve efficacy but increases cost, inconvenience, and adverse effects. We aimed to evaluate if less than 1 year of adjuvant trastuzumab retained efficacy while reducing toxicities and cost.

Methods: We performed a pooled analyses of efficacy and toxicity from Randomized Controlled Trials (RCTs) comparing 1 year of trastuzumab to shorter durations in adjuvant treatment of HER2-positive breast cancer. Hazard Ratios (HR) for Overall Survival (OS) and Disease-Free Survival (DFS), and Odds Ratios (OR) for cardiac events with respective 95% Confidence Intervals (CI) were weighted using generic inverse variance approach and pooled in meta-analyses using random effects models with RevMan 5.3 software. Sub-group analyses of outcomes based on Estrogen Receptor (ER) and nodal status were performed.

Results: Five RCTs involving approximately 12,000 patients qualified-three assessing 6 months and two assessing 9 weeks of trastuzumab compared to 1 year. All RCTs were designed to test non-inferiority of the shorter treatment. One year of trastuzumab resulted into better OS (pooled HR 1.23, 95% CI 1.07-1.42) and DFS (pooled HR 1.21, 95% CI 1.09-1.36) in overall population, but the benefit of longer treatment was statistically insignificant in node negative (HR 1. 20, p = 0.11), and ER positive disease (HR 1.15, p = 0.09). Odds ratio for cardiac events was significantly higher with the longer duration (OR 2.48, p < 0.001).

Conclusion: One year of trastuzumab for adjuvant treatment of breast cancer improves outcomes compared to shorter treatments in overall population. Cardiotoxicity is increased with the longer treatment.

Keywords: Adjuvant; Breast cancer; Duration; Herceptin.