Overcoming resistance to endocrine therapy in hormone receptor-positive human epidermal growth factor receptor 2-negative (HR+/HER2--) advanced breast cancer: a meta-analysis and systemic review of randomized clinical trials
Wenjie Zhu, Binghe Xu()
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing 100021, China
New targeted therapies have been developed to overcome resistance to endocrine therapy (ET) and improve the outcome of HR+/HER2-- advanced breast cancer (ABC). We conducted a meta-analysis and systemic review on randomized controlled trials evaluating various targeted therapies in combination with ET in HR+/HER2-- ABC. PUBMED and EMBASE databases were searched for eligible trials. Hazard ratios (HRs) for progression-free survival (PFS), odds ratios (ORs) for objective response rate (ORR), clinical benefit rate (CBR), and toxicity were meta-analyzed. Twenty-six studies with data on 10 347 patients were included and pooled. The addition of cyclin-dependent kinase 4/6 inhibitors to ET significantly improved median PFS (pooled HR= 0.547, P<0.001), overall survival (pooled HR= 0.755, P<0.001), and tumor response rates (ORR, pooled OR= 1.478, P<0.001; CBR, pooled OR= 1.201, P<0.001) with manageable toxicities (pooled OR= 3.280, P<0.001). The mammalian targets of rapamycin inhibitors and exemestane were not clinically beneficial for this pooled population including ET-naïve and ET-resistant patients. Moderate improvement in PFS (pooled HR= 0.686, P<0.001) yet pronounced toxicities (pooled OR=2.154, P<0.001) were noted in the combination of phosphatidylinositol-4,5-bisphosphate 3-kinase inhibitors with fulvestrant. Future studies are warranted to optimize the population and the dosing sequence of these available options.
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