Background: Trastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor-2 targeted antibody-drug conjugate that contains a monoclonal antibody, trastuzumab, covalently linked to DM1, a small molecule cytotoxin.
Methods: We conducted a systematic review and meta-analysis of published trials to examine the efficacy and safety of T-DM1 for patients with HER2-positive metastatic breast cancer. In addition, we systematically reviewed existing economic evaluations of T-DM1. An electronic literature search of online databases (Medline, CENTRAL, and Embase) was performed. Randomized controlled trials that compared T-DM1 with other active treatment agents were eligible for inclusion. In addition, studies that involved T-DM1 as one of the treatment comparators in an economic evaluation were included. Four trials with a total of 2462 participants were included in this meta-analysis.
Results: Pooled results showed T-DM1 substantially improved overall survival (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.67-0.85; I2 = 0%) and progression-free survival (HR, 0.67; 95% CI, 0.52-0.85; I2 = 75%). In addition, T-DM1 showed greater association with severe thrombocytopenia and liver dysfunction than other regimens, but a lower rate of neutropenia, leukopenia, febrile neutropenia, asthenia, and diarrhea. All four trials included in the meta-analysis overall had a low risk of bias. Two cost-utility analyses involving T-DM1 were identified, and the overall quality was high.
Conclusions: T-DM1 is effective for the treatment of patients with HER2-positive metastatic breast cancer, and it demonstrates a tolerable safety profile compared with other active controls. Little evidence was available regarding the cost-effectiveness of T-DM1 so no conclusions can be drawn.
Keywords: HER2-positive metastatic; cost-effectiveness; effectiveness; meta-analysis; trastuzumab emtansine.