Updates on managing advanced breast cancer with palbociclib combination therapy.
Updates on managing advanced breast cancer with palbociclib combination therapy.
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DOI：
10.1177/1758835918793849
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发表时间：
2018
影响因子：
4.9
通讯作者：
Ryan JC
中科院分区：
文献类型：
--
作者：
McShane TM;Wolfe TA;Ryan JC
本研究的目的是审查palbociclib（一种一流的细胞周期蛋白依赖性激酶4/6抑制剂）治疗晚期乳腺癌（ABC）的药理学、疗效和安全性。描述了与palbociclib相关的药代动力学和药物相互作用。最近的临床试验数据进行审查，包括患者报告的结果和亚组分析。Palbociclib适用于与芳香酶抑制剂联合作为初始内分泌治疗（ET），或与氟维司群联合用于ET后疾病进展的激素受体阳性、人表皮生长因子受体2阴性ABC或转移性乳腺癌患者。Palbociclib可抑制细胞周期蛋白依赖性激酶4/6，从而阻断视网膜母细胞瘤蛋白的磷酸化，从而阻碍参与S期进入的转录因子的激活，从而将细胞周期进程阻滞在G1期。在三项随机试验（PALOMA-1、-2和-3）中确定了Palbociclib联合ET的疗效和安全性;所有研究均达到了主要终点，即与ET单药治疗相比，经药物评估的无进展生存期显著延长。三项PALOMA研究的亚组分析结果相似。在PALOMA-2和-3中，与ET单药治疗相比，Palbociclib + ET治疗还维持了健康相关的生活质量（QoL）。已确立了palbociclib长达3年的长期安全性特征。中性粒细胞增多症是与palbociclib相关的最常见的任何级别和3级或3级以上不良事件，与药物的作用机制一致，可以通过中断剂量、减少剂量或延迟开始治疗周期进行有效管理。Palbociclib联合ET可改善ABC患者的无进展生存期和QoL，包括多个患者亚组。
The objective of this study was to review the pharmacology, efficacy, and safety of palbociclib, a first-in-class cyclin-dependent kinase 4/6 inhibitor, for the management of advanced breast cancer (ABC). Pharmacokinetics and drug interactions associated with palbociclib are described. Recent clinical trial data are reviewed, including patient-reported outcomes and subgroup analyses. Palbociclib is indicated in combination with an aromatase inhibitor as initial endocrine therapy (ET) or with fulvestrant for patients with disease progression following ET for hormone receptor positive, human epidermal growth factor receptor 2 negative ABC or metastatic breast cancer. Palbociclib inhibits cyclin-dependent kinases 4/6, resulting in a blockade of phosphorylation of the retinoblastoma protein, which hinders the activation of transcription factors involved in S-phase entry, thereby arresting cell cycle progression at G1 phase. The efficacy and safety of palbociclib in combination with ET was established in three randomized trials (PALOMA-1, -2, and -3); all studies met their primary endpoint of significantly prolonging investigator-assessed progression-free survival versus ET alone. Findings were similar in subgroup analyses of the three PALOMA studies. Palbociclib plus ET also maintained health-related quality of life (QoL) compared with ET alone in PALOMA-2 and -3. A long-term safety profile for palbociclib, up to 3 years, has been established. Neutropenia, the most common any-grade and grade 3 or higher adverse event associated with palbociclib, is consistent with the drug’s mechanism of action and can be effectively managed with dose interruption, dose reduction, or delay in starting treatment cycles. Palbociclib in combination with ET improved progression-free survival and QoL in patients with ABC, including in several patient subgroups.
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影响因子：
11.5
作者：
Flaherty, Keith T.;LoRusso, Patricia M.;Schwartz, Gary K.
通讯作者：
Schwartz, Gary K.
影响因子：
11.5
作者：
Hu, Wenyue;Sung, Tae;Sacaan, Aida I.
通讯作者：
Sacaan, Aida I.
影响因子：
51.1
作者：
Finn, Richard S.;Crown, John P.;Slamon, Dennis J.
通讯作者：
Slamon, Dennis J.
影响因子：
18.2
作者：
Campisi J
通讯作者：
Campisi J
DOI：
10.1186/s13058-016-0721-5
发表时间：
2016-06-28
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Finn RS;Crown JP;Ettl J;Schmidt M;Bondarenko IM;Lang I;Pinter T;Boer K;Patel R;Randolph S;Kim ST;Huang X;Schnell P;Nadanaciva S;Bartlett CH;Slamon DJ
通讯作者：
Slamon DJ