Herceptin® (trastuzumab) in HER2-positive early breast cancer: a systematic review and cumulative network meta-analysis

Background: Originator trastuzumab (Herceptin (R); H) is an antibody-targeted therapy to treat patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (EBC). We investigated the overall survival (OS) advantage conferred by the addition of H to chemotherapy for HER2+ EBC patients and how the OS advantage changed over time. Methods: A systematic literature review (SLR) identified randomized controlled trials (RCTs) and non-randomized studies (NRSs) published from January 1, 1990 to January 19, 2017, comparing systemic therapies used in the neoadjuvant/adjuvant settings to treat HER2+ EBC patients. Bayesian cumulative network meta-analyses (cNMAs) of OS were conducted to assess the published literature over time. Heterogeneity was assessed through sensitivity and subgroup analyses. Results: The SLR identified 31 unique studies (28 RCTs, 3 NRSs) included in the OS analyses from 2008 to 2016. In the reference case cNMA (RCTs alone), initial evidence demonstrated an OS advantage for H/chemotherapy compared with chemotherapy alone in HER2+ EBC patients. As additional OS data were published, the precision around this survival benefit strengthened over time. Both H/anthracycline-containing chemotherapy and H/non-anthracyclinecontaining chemotherapy regimens provided similar OS advantages for HER2+ EBC patients. Conclusion: This analysis represents the most comprehensive SLR/cNMA to date of published OS data in HER2+ EBC studies. These findings demonstrate why H/chemotherapy is now the established standard of care in HER2+ EBC. In the case of H, the benefits of early patient access far outweighed the risk of waiting for more precise information.