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

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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.

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Authors and Affiliations

  1. Section of Medical Oncology and Hematology, Department of Internal Medicine, University of Manitoba and CancerCare Manitoba, Winnipeg, MB, Canada

    Saroj Niraula

  2. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Bishal Gyawali

Authors
  1. Saroj Niraula
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  2. Bishal Gyawali
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Corresponding author

Correspondence to Saroj Niraula.

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Conflict of interest

Institutional research grant from Pfizer (SN). Neither of the authors have personal conflict of interest.

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Niraula, S., Gyawali, B. Optimal duration of adjuvant trastuzumab in treatment of early breast cancer: a meta-analysis of randomized controlled trials. Breast Cancer Res Treat 173, 103–109 (2019). https://doi.org/10.1007/s10549-018-4967-8

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  • DOI: https://doi.org/10.1007/s10549-018-4967-8

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