Efficacy, safety and administration timing of trastuzumab in human epidermal growth factor receptor 2 positive breast cancer patients: A meta-analysis.

Trastuzumab has been demonstrated to be an effective treatment in patients with human epidermal growth factor receptor-2 (HER-2) positive breast cancer (BC); however, inconsistent results with regards to the long-term survival benefits, safety and optimal administration timing of trastuzumab exist. The present meta-analysis investigated these inconsistencies in patients with HER-2 positive BC that received adjuvant or neoadjuvant trastuzumab. Computerized and manual searches were used to identify eligible randomized control trials (RCTs) to include in the analysis. Based on a fixed or random effects model, hazard and risk ratios were calculated and used to assess the survival advantages and risks of trastuzumab. A total of 14,546 patients from 13 RCTs were included in the analysis; 9 RCTs used an adjuvant setting and 4 RCTs used a neoadjuvant setting. Analysis of RCTs with an adjuvant setting demonstrated that treatment with trastuzumab and chemotherapy in patients with HER-2 positive BC, in comparison with patients receiving chemotherapy alone, improved disease-free survival, overall survival and overall response. However, a higher incidence of neutropenia (P<0.0001), leukopenia (P<0.0001), diarrhea (P=0.002), skin/nail change (P=0.02), left ventricular ejection fraction reduction (P=0.007) and congestive heart failure (P<0.00001) was observed. Notably, the incidence of mortality and cardiac toxicity following concurrent and weekly use of trastuzumab was significantly lower compared to treatment with trastuzumab sequentially and every 3 weeks, respectively. Additionally, trastuzumab improved the pathologic complete response with no additional toxicity in the neoadjuvant setting. The present meta-analysis summarizes that trastuzumab is efficacious in patients with HER-2 positive BC in adjuvant and neoadjuvant settings. Thus, concurrent and weekly administration of trastuzumab is preferable to treatment with trastuzumab sequentially and every 3 weeks. These findings should be considered when using trastuzumab in future clinical practice.