期刊
CLINICAL BREAST CANCER
卷 20, 期 1, 页码 1-11出版社
CIG MEDIA GROUP, LP
DOI: 10.1016/j.clbc.2019.06.017
关键词
Cyclin dependent kinase 4/6 inhibition; Endocrine resistance; ESR1 mutations; PIK3CA mutations
类别
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with backbone endocrine therapy have markedly improved progression-free survival and overall survival over endocrine therapy alone in advanced hormone receptor epositive, HER2-negative (HR+/HER2(-)) breast cancer and are the standard of care in the first- or second-line setting. There are few data to drive decision making for subsequent treatment strategies after inevitable disease progression after CDK4/6i. Information about the genomic landscape of CDK4/6i-resistant disease is emerging. Resistance mechanisms appear to be varied, but mutations in PIK3CA and ESR1, which can be acquired while receiving treatment, are frequent. Activating PIK3CA mutations are present in up to 35% of patients and are now the most actionable genomic alteration in HR+/HER2(-) advanced breast cancer with the recent approval of alpelisib and fulvestrant. Everolimus-based combinations and chemotherapy appear to have continued efficacy after progression while receiving CDK4/6i, although historical data on benefit include CDK4/6i-naive patients. Use of selective estrogen down-regulators over aromatase inhibitors is best once the patient has an acquired ESR1 mutation. Tumor biopsy with genomic sequencing and repeat biomarker analysis in patients with CDK4/6i- and endocrine-resistant disease will be integral to guide subsequent treatment strategies and to inform clinical trial eligibility. Promising novel therapeutics in CDK4/6i-resistant disease including oral selective estrogen down-regulators, fibroblast growth factor receptor antagonists, and immunotherapy will be discussed.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据