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

Abstract

PurposeTo investigate the efficacy and safety of doublet versus single-agent chemotherapy (CT) plus trastuzumab (H) as first-line therapy for human epidermal growth factor 2 receptor (HER2)-positive metastatic breast cancer (MBC).MethodsWe searched for randomized clinical trials (RCTs) that evaluated the treatment effects of single-agent or doublet CT+H as first-line therapies for HER2-positive MBC. The main outcomes measured for this study included the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). A meta-analysis and trial sequential analysis (TSA) were performed, and the study quality was evaluated using the GRADE framework. The PROSPERO registry number of our analysis is CRD42016043766.ResultsThe results from four RCTs including 1044 participants were pooled. Moderate-quality evidence indicated that compared with single-agent CT+H, doublet CT+H correlated better with prolonged PFS (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.63–0.75, P < 0.0001) and OS (HR = 0.90, 95% CI 0.88–0.92, P < 0.0001). However, moderate-quality evidence revealed no significant difference between the two regimens regarding the ORR (relative risk [RR] = 1.07, 95% CI 0.98–1.17, P = 0.157), which was confirmed by TSA, indicating that the cumulative Z-curve entered the futility area. Moderate-quality evidence indicated that treatment-related grade 3 or 4 toxicities of thrombocytopenia (RR = 4.08, P = 0.000), nausea/vomiting (RR = 4.26, P = 0.002), diarrhea (RR = 2.81, P = 0.002), and stomatitis (RR = 5.02, P = 0.003) were observed more frequently with doublet CT+H than with single-agent CT+H.ConclusionsCompared with single-agent CT, the combination of doublet CT with trastuzumab as first-line therapy for HER2-positive MBC is associated with longer PFS and OS, but more treatment-related grade 3 or 4 toxicities. Therefore, doublet CT appears to be an appropriate regimen for HER2-positive MBC with a good performance status.Electronic supplementary materialThe online version of this article (10.1007/s10549-017-4592-y) contains supplementary material, which is available to authorized users.

Clinical Evidence of Chemotherapy or Endocrine Therapy Maintenance in Patients with Metastatic Breast Cancer: Meta-Analysis of Randomized Clinical Trials and Propensity Score Matching of Multicenter Cohort Study

“…We included several new trials [3,5,18,21] that were not included in the previous study [22], in particular studies that included new antitumor drugs including gemcitabine and capecitabine. A meta-analysis [23] included four RCTs with 1,044 participants and found that the combination of doublet chemotherapy with trastuzumab compared with single-agent chemotherapy as first-line therapy for human epidermal growth factor receptor (HER2)-positive MBC is associated with longer PFS and OS, and recommended that doublet chemotherapy appears to be an appropriate regimen for good performance status patients. This meta-analysis with multicentre cohort study findings support PFS and OS benefit of chemotherapy than observation after first-line chemotherapy in MBC.…”

Analysis of the metastatic mechanism and progress in the treatment of breast cancer liver metastasis: a narrative review

“…Moreover, studies on single-agent vs. double-agent chemotherapy combined with trastuzumab for the treatment of HER2-positive MBC had mixed results ( 48 ). To resolve this contradiction, a meta-analysis by Yu et al ( 49 ) showed that the PFS and OS of patients with HER2-positive MBC treated with dual-drug chemotherapy combined with trastuzumab were better, but the treatment-related toxicity was more severe. BCLM can cause liver function damage, so the scope of application of dual-drug chemotherapy combined with trastuzumab needs to be explored in relevant clinical trials.…”