Trastuzumab combined with doublet or single-agent chemotherapy as a first-line treatment for HER2-positive metastatic breast cancer.

e12511 Background: To investigate the efficacy and safety of doublet vs. single-agent chemotherapy (CT) plus trastuzumab as first-line treatments for human epidermal growth factor 2 receptor (HER2)-positive metastatic breast cancer (MBC). Methods: We searched for randomized clinical trials (RCTs) that investigated the treatment effects of single-agent or doublet CT+H as first-line therapies for HER2-positive MBC. The main outcome measures for this analysis included the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Meta-analyses and trial sequential analyses (TSA) were conducted. The study quality was evaluated using the GRADE framework. The PROSPERO registry number is CRD42016043766. Results: The results from four RCTs that included 1,044 participants were pooled. Moderate-quality evidence indicated that doublet CT+H better correlated with prolonged PFS (hazard ratio [HR] = 0.69, 95% confidence interval (CI) 0.63 to 0.75, P < 0.0001) and OS (HR = 0.90, 95% CI 0.88 to 0.92, P < 0.0001) than did single-agent CT+H; however, moderate-quality evidence indicated there was no significant difference between the two drug regimens regarding the ORR (relative risk [RR] = 1.07, 95% CI 0.98 to 1.17, P = 0.157), as confirmed by TSA, which indicated that the cumulative Z-curve entered the futility area. There was moderate-quality evidence that the treatment-related grade 3 to 4 toxicities of thrombocytopenia (RR = 4.08, P = 0.000; number needed to treat to harm (NNTH) = 20), nausea/vomiting (RR = 4.26, P = 0.002; NNTH = 25), diarrhea (RR = 2.81, P = 0.002; NNTH = 25), and stomatitis (RR = 5.02, P= 0.003; NNTH = 25) were more frequent with doublet CT+H than single-agent CT+H. Conclusions: Doublet CT+H is associated with longer PFS and OS than single-agent CT+H when used as a first-line therapy for HER2-positive MBC.