帕博西利布
医学
富维斯特朗
转移性乳腺癌
细胞周期蛋白依赖激酶
乳腺癌
肿瘤科
细胞周期蛋白依赖激酶4
临床试验
药理学
内科学
癌症
细胞周期
雌激素受体
细胞周期蛋白依赖激酶2
作者
Amy S. Clark,Thomas B. Karasic,Angela DeMichele,David J. Vaughn,Mark H. O’Hara,Rodolfo F. Perini,Paul Zhang,Priti Lal,Michael D. Feldman,Maryann Gallagher,Peter J. O’Dwyer
出处
期刊:JAMA Oncology
[American Medical Association]
日期:2016-02-01
卷期号:2 (2): 253-253
被引量:98
标识
DOI:10.1001/jamaoncol.2015.4701
摘要
Importance
Palbociclib (PD0332991) is a newly developed drug that received breakthrough designation and recent US Food and Drug Administration approval in combination with endocrine therapy in the treatment of hormone receptor positive, ERBB2-negative (formerly HER2 or HER2/neu) breast cancer in the first-line metastatic setting. Objective
Herein we describe the preclinical and translational data and early- and late-phase clinical trials in which palbociclib has been investigated in a broad array of tumor types. We discuss the pharmacodynamics, pharmacokinetics, toxic effects, and clinical response rates. Evidence Review
On March 1, 2015, we conducted a review of the literature describing the development of palbociclib. We used the PubMed search terms “PD0332991,” “palbociclib,” and “CDK4/6 inhibitor” to find all published articles of interest, without limitation as to publication date. Findings
Palbociclib is a potent and specific oral cyclin-dependent kinase (CDK) 4/6 inhibitor that has strong preclinical data to support its activity in retinoblastoma protein–expressing tumors. Phase 1 trials have demonstrated safety, and phase 2 trials have shown single-agent activity in mantle-cell lymphoma, breast cancer, liposarcoma, and teratoma with reversible neutropenia as the main toxic effect. Addition of palbociclib to endocrine therapy improves progression-free survival in endocrine therapy–naïve and endocrine therapy–resistant metastatic settings. Conclusions and Relevance
Palbociclib is well tolerated and has therapeutic potential for multiple cancers, including breast cancer, where its efficacy has been demonstrated alone and in combination with endocrine therapy. Additional combinations of palbociclib with endocrine therapy, chemotherapy, and targeted therapy have potential in various tumors, and phase 3 trials are under way.
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