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.

Abstract	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.
Authors	Wenjie Zhu, Binghe Xu
Journal	Frontiers of medicine (Front Med) Vol. 15 Issue 2 Pg. 208-220 (Apr 2021) ISSN: 2095-0225 [Electronic] China
PMID	33175319 (Publication Type: Journal Article, Meta-Analysis, Review, Systematic Review)
Chemical References	Hormones Receptors, Estrogen ERBB2 protein, human Receptor, ErbB-2
Topics	Antineoplastic Combined Chemotherapy Protocols (therapeutic use) Breast Neoplasms (drug therapy) Hormones Humans Randomized Controlled Trials as Topic Receptor, ErbB-2 Receptors, Estrogen

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