Trastuzumab in the Adjuvant Treatment of Early-Stage Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Abstract Learning Objectives After completing this course, the reader will be able to: Summarize the main characteristics and findings of randomized controlled trials evaluating trastuzumab for the adjuvant treatment of early-stage breast cancer.Use combined-effect estimates provided by meta-analysis to appraise the risks and benefits of trastuzumab treatment in the adjuvant setting.Identify the links between basic science and drug development that led to the successful clinical use of trastuzumab, as well as the gaps in the existing evidence base regarding its use in breast cancer treatment. CME This article is available for continuing medical education credit at CME.TheOncologist.com Background. We performed a systematic review and meta-analysis to compare treatment outcomes for human epidermal growth factor receptor (HER)-2–positive breast cancer patients receiving adjuvant chemotherapy with or without trastuzumab. Methods. We identified randomized clinical trials comparing adjuvant chemotherapy with or without trastuzumab in patients with resectable breast cancer. Fixed-effects meta-analysis was used to combine data. Results. Five eligible trials were identified, reporting outcomes on 13,493 women. Fixed-effects analysis showed disease-free survival to be superior for trastuzumab-treated patients (risk ratio [RR], 0.62; 95% confidence interval [CI], 0.56–0.68). Superiority was also observed for patients receiving trastuzumab with respect to mortality (RR, 0.66; 95% CI, 0.57–0.77), locoregional recurrence (RR, 0.58; 95% CI, 0.43–0.77), and distant recurrence (RR, 0.60; 95% CI, 0.52–0.68). Patients receiving trastuzumab with chemotherapy had a higher risk for congestive heart failure (RR, 7.60; 95% CI, 4.07–14.18) and left ventricular ejection fraction decline (RR, 2.09; 95% CI, 1.84–2.37). A higher risk for central nervous system metastasis as the first recurrence event (RR, 1.60; 95% CI, 1.06–2.40) was also noted in patients receiving trastuzumab. Conclusions. The use of trastuzumab should be considered an integral part of the adjuvant therapy of HER-2–positive breast cancer patients.