Effectiveness of Added Targeted Therapies to Neoadjuvant Chemotherapy for Breast Cancer: A Systematic Review and Meta-analysis

Over the past several years, targeted therapy has been increasingly used in the management of breast cancer. Reported results for targeted therapies are variable, as some randomized controlled trials (RCTs) reported a strong effect, whereas others reported no or minimal effect on the outcomes. Accordingly, the present study aimed to assess the effect of the addition of targeted therapies to neoadjuvant chemotherapy on tumor response rates, breast conserving surgeries, and survival outcomes. PubMed and the Cochrane register of clinical trials were searched on April 28, 2017 for RCTs comparing addition of targeted therapies to neoadjuvant chemotherapy. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the screening of records and data extraction were performed by 2 independent reviewers. Publication bias and risk of bias were assessed by the Egger test and the Cochrane tool for risk of bias assessment, respectively. The fixed effect method or random effect method were used to synthesize the results depending on the heterogeneity assessed by the I2 statistic. A total of 17 RCTs including trastuzumab (n = 5), bevacizumab (n = 7), and other targeted therapies (n = 5) were found eligible. Pathologic complete response was significantly higher with trastuzumab (relative risk [RR], 2.20; 95% confidence interval [CI], 1.62-2.99) and bevacizumab (RR, 1.23; 95% CI, 1.11-1.37), but not with other targeted therapies. Bevacizumab for human epidermal growth factor receptor 2 (HER2)-negative breast cancer was found to be associated with improved overall (hazard ratio, 0.69; 95% CI, 0.53-0.90) and disease-free survival (hazard ratio, 0.83; 95% CI, 0.6-71.03). The addition of targeted therapies may not significantly increase breast conserving surgery rates (RR, 1.04; 95% CI, 0.97-1.12). The addition of targeted therapies, especially trastuzumab for patients with HER2-positive breast cancer and bevacizumab for patients with HER2-negative breast cancer significantly increased pathologic complete response, overall response, and clinical complete response but not breast conserving surgery rates. (C) 2019 Elsevier Inc. All rights reserved.