A network meta-analysis on the efficacy of HER2-targeted agents in combination with taxane-containing regimens for treatment of HER2-positive metastatic breast cancer.

Objective: We performed a network meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of HER2-targeted agents in combination with taxanes and to identify the best strategy for HER2+ metastatic breast cancer (MBC).

Methods: Pubmed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials that evaluated any taxanes+HER2-targeted agents in the treatment of HER2+ MBC. The primary outcome was overall survival (OS). The secondary outcomes included overall response rate (ORR) and progression-free survival (PFS).

Results: A total of 13 RCTs were eligible, involving 4941 patients and 10 regimens. The result showed that single-HER2-targeted agent+a taxane did improve the effect on ORR and PFS than taxane alone, but only trastuzumab+a taxane had a significant improvement in OS outcomes. Single-HER2-targeted agent (trastuzumab) combined with taxane-based doublets (taxane+carboplatin/capecitabine/doxorubicin/bevacizumab) showed no further benefit than trastuzumab+a taxane. Doublet-HER2-targeted agents combined with a taxane(trastuzumab+pertuzumab+a taxane) showed further improvement in ORR, PFS, and all OS outcomes than single-HER2-targeted agent+a taxane. Ranking analysis based on their P-scores suggested that trastuzumab+pertuzumab+a taxane was the best combination treatment for all the efficacy outcomes.

Conclusions: These findings demonstrate that combining two HER2-targeted agents (trastuzumab+pertuzumab) with a taxane is much more beneficial for the treatment of HER2+ MBC. Dual HER2-targeted agents combined with a taxane appears to be the preferred application of HER2+ MBC.