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

BackgroundOne 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 1year of adjuvant trastuzumab retained efficacy while reducing toxicities and cost.MethodsWe performed a pooled analyses of efficacy and toxicity from Randomized Controlled Trials (RCTs) comparing 1year 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.ResultsFive RCTs involving approximately 12,000 patients qualifiedthree assessing 6months and two assessing 9weeks of trastuzumab compared to 1year. All RCTs were designed to test non-inferiority of the shorter treatment. One year of trastuzumabresulted 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 statisticallyinsignificant 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).ConclusionOne 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.