Effect of pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer: A meta-analysis

Introduction: Pertuzumab, as an adjunctive therapy to trastuzumab and docetaxel, has been reported to be potentially beneficial for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. However, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of pertuzumab supplementation in patients with HER2-positive metastatic breast cancer. Methods: Medline, SCOPUS, Google Scholar, Cochrane library databases, EMBASE, Springer, and Science Direct were systematically searched. Randomized controlled trials (RCTs) assessing the effect of pertuzumab + trastuzumab + docetaxel vs. trastuzumab + docetaxel on the treatment of HER2-positive metastatic breast cancer were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcomes were death, overall survival, and progression-free survival. Meta-analysis was performed using fixed-or random-effect model. Results: Five RCTs involving 3,742 patients were included in the meta-analysis. Overall, compared with placebo and trastuzumab + docetaxel treatment, combination treatment of pertuzumab + trastuzumab + docetaxel treatment was associated with the significantly reduced death (hazard ratio (HR) = 0.67; 95% confidence interval (CI) = 0.57 -0.78; p < 0.005) as well as improved overall survival (HR = 0.66; 95% CI = 0.35 -0.67; p = 0.98) and progression-free survival (HR = 0.64; 95% CI = 0.58 -0.71; p < 0.005). Moreover, pertuzumab supplementation did not increase the number of patients with reductions in the left ventricular ejection fraction (LVEF) of 10% or more (risk ratio (RR) = 0.70; 95% CI = 0.47 -1.04; p = 0.07). Conclusion: Pertuzumab + trastuzumab + docetaxel treatment significantly reduced death, increased overall survival, and progression-free survival in patients with HER2-positive metastatic breast cancer compared to placebo and trastuzumab + docetaxel treatment, but showed no increased adverse events.