Trastuzumab‐containing regimens for metastatic breast cancer

Background Patients with breast cancer are classified as having cells that over‐express the human epidermal growth factor receptor 2 (known as HER2‐positive) or not (HER2‐negative). Typically, patients with HER2‐positive disease have a worse prognosis. Trastuzumab is a selective treatment that targets the HER2 pathway. The available evidence supporting trastuzumab regimens mostly relies upon surrogate endpoints and, although the efficacy results seem to support its use, other uncertainties have been raised about its net benefit in relation to transient cardiac toxicity and a long‐term increased risk of metastasis to the central nervous system. Objectives To assess the evidence on the efficacy and safety of therapy with trastuzumab (overall) and in relation to the type of co‐administered regimen and the line of treatment, i.e. first‐line or beyond progression, in women with HER2‐positive metastatic breast cancer. Search methods We searched the Cochrane Breast Cancer Group's (CBCG) Specialised Register and used the search strategy developed by the CBCG to search for randomised controlled trials (RCTs) in CENTRAL (2013, Issue 1), MEDLINE, EMBASE, BIOSIS, the WHO International Clinical Trials Registry Platform (ICTRP) search portal and ClinicalTrials.gov (up to 17 January 2013). Selection criteria RCTs comparing the efficacy and safety of trastuzumab alone or in combination with chemotherapy, hormonal therapy or targeted agents in women with HER2‐positive metastatic breast cancer. Data collection and analysis We collected data from published trials. We used hazard ratios (HRs) for time‐to‐event outcomes and risk ratio (RRs) for binary outcomes. Subgroup analyses included type of regimen (taxane‐containing, anthracycline‐containing, aromatase inhibitor‐containing or other) and treatment line (first‐line, beyond progression). Main results The review found seven trials, involving 1497 patients, which met the criteria to be included. The trials were generally of moderate methodological quality; two studies have not published their results on overall survival so the presence of selective outcome reporting bias cannot be ruled out. None of the studies used blinding to treatment allocation, though this is unlikely to have biased the results for overall survival. Studies varied in terms of co‐administered regimen and in terms of treatment line. In four studies, trastuzumab was administered with a chemotherapy, such as a taxane‐containing, anthracycline‐containing or c