Abstract
e13023 Background: Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-positive breast cancer is a distinct subtype with different prognosis and response to treatment. HER2-targeted therapy is currently recommended for patients with HR+/HER2+ advanced breast cancer. However, there is debate over which drugs to add on the basis of HER2 blockade yields the optimal efficacy. Moreover, the research on replacing chemotherapy with endocrine therapy in the regimens are under way. This systematic review and network meta-analysis was conducted to find the optimal treatment for this subtype. Methods: Eligible randomized controlled trials (RCTs) comparing different interventions in metastatic HR+/HER2+ breast cancer were included by comprehensively searching PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, and abstracts of oncology conferences before September 5th, 2022. The outcomes of interest included progression free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAEs). Pooled hazard ratios (HRs) or odds ratios (ORs) with credible intervals (CrIs) were calculated to estimate the predefined outcomes based on the data type. The optimal therapeutics were identified by utilizing the cumulative ranking curves (SUCRA). Results: In total, 23 pieces of literature of 20 RCTs were included. Regarding PFS, significant differences were detected between dual HER2 blockade plus endocrine therapy versus endocrine therapy alone (HR 0.45, 95% CrI 0.25-0.83; HR 0.47, 95% CrI 0.27-0.87), and trastuzumab, pertuzumab plus chemotherapy versus trastuzumab plus chemotherapy (HR 0.69, 95% CrI 0.47-0.96). The SUCRA values suggested the relatively better efficacy of dual HER2-targeted therapy plus endocrine therapy (86% to 91%) or chemotherapy (62% to 81%) in prolonging PFS and OS. The HER2 blockade-containing regimens showed similar safety profiles in eight documented TRAEs. Conclusions: Prominent status of dual-targeted therapy for patients with HR+/HER2+ metastatic breast cancer was revealed. Compared with chemotherapy-containing regimens, the endocrine therapy-containing regimens showed better efficacy and similar safety profile, which could be recommended in practice.
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