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Cancer Cell. 2020 Apr 13;37(4):514-529. doi: 10.1016/j.ccell.2020.03.010.
2
Palbociclib added to ongoing endocrine therapy for hormone receptor-positive HER2-negative metastatic breast cancer: A case report series.帕博西尼联合正在进行的内分泌治疗用于激素受体阳性、人表皮生长因子受体2阴性转移性乳腺癌:病例报告系列
Mol Clin Oncol. 2020 May;12(5):456-460. doi: 10.3892/mco.2020.2016. Epub 2020 Mar 11.
3
Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): a multicentre, open-label, randomised, phase 2 trial.帕博西尼联合戈舍瑞林与卡培他滨用于激素受体阳性、HER2 阴性转移性乳腺癌绝经前妇女(KCSG-BR15-10):一项多中心、开放标签、随机、2 期临床试验。
Lancet Oncol. 2019 Dec;20(12):1750-1759. doi: 10.1016/S1470-2045(19)30565-0. Epub 2019 Oct 24.
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Multiple effects of CDK4/6 inhibition in cancer: From cell cycle arrest to immunomodulation.CDK4/6 抑制在癌症中的多重作用:从细胞周期阻滞到免疫调节。
Biochem Pharmacol. 2019 Dec;170:113676. doi: 10.1016/j.bcp.2019.113676. Epub 2019 Oct 21.
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Trilaciclib plus chemotherapy versus chemotherapy alone in patients with metastatic triple-negative breast cancer: a multicentre, randomised, open-label, phase 2 trial.特立西布联合化疗对比单独化疗治疗转移性三阴性乳腺癌患者的多中心、随机、开放标签、二期临床试验。
Lancet Oncol. 2019 Nov;20(11):1587-1601. doi: 10.1016/S1470-2045(19)30616-3. Epub 2019 Sep 28.
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Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis.绝经后激素受体阳性、HER2 阴性转移性乳腺癌患者的内分泌治疗与化疗:系统评价和网络荟萃分析。
Lancet Oncol. 2019 Oct;20(10):1360-1369. doi: 10.1016/S1470-2045(19)30420-6. Epub 2019 Sep 4.
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Combination Paclitaxel and Palbociclib: Results of a Phase I Trial in Advanced Breast Cancer.紫杉醇联合帕博西利治疗晚期乳腺癌的 I 期临床试验结果。
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8
Randomized Phase II Study Evaluating Palbociclib in Addition to Letrozole as Neoadjuvant Therapy in Estrogen Receptor-Positive Early Breast Cancer: PALLET Trial.随机 II 期研究评估帕博西尼联合来曲唑作为雌激素受体阳性早期乳腺癌新辅助治疗:PALLET 试验。
J Clin Oncol. 2019 Jan 20;37(3):178-189. doi: 10.1200/JCO.18.01624. Epub 2018 Dec 6.
9
Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer.哌柏西利联合氟维司群治疗晚期乳腺癌的总生存期
N Engl J Med. 2018 Nov 15;379(20):1926-1936. doi: 10.1056/NEJMoa1810527. Epub 2018 Oct 20.
10
Letrozole and palbociclib versus chemotherapy as neoadjuvant therapy of high-risk luminal breast cancer.来曲唑联合帕博西利对比化疗用于高危型 luminal 乳腺癌的新辅助治疗。
Ann Oncol. 2018 Dec 1;29(12):2334-2340. doi: 10.1093/annonc/mdy448.

帕博西尼作为一种乳腺癌治疗选择的评估:最新进展。

An evaluation of palbociclib as a breast cancer treatment option: a current update.

机构信息

Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University, School of Medicine , Washington, DC, USA.

Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital , Washington, DC, USA.

出版信息

Expert Opin Pharmacother. 2021 Feb;22(3):281-290. doi: 10.1080/14656566.2020.1838485. Epub 2020 Nov 16.

DOI:10.1080/14656566.2020.1838485
PMID:33198527
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7897260/
Abstract

INTRODUCTION

Patients with hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer have benefitted from treatment with palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor capable of selectively targeting mechanisms of cell cycle progression that contribute to tumor cell proliferation. Palbociclib use in this setting demonstrates improved progression-free survival when given in combination with aromatase inhibitors or fulvestrant.

AREAS COVERED

The authors describe the current state of research surrounding palbociclib use in breast cancer, present evidence supporting a role for palbociclib in additional subtypes of metastatic breast cancer such as HER2-positive (HER2+) and triple-negative, report ongoing clinical trials aimed at expanding the scope of use for palbociclib, and discuss expected clinical results that will better inform decisions on including palbociclib as a part of breast cancer treatment strategies.

EXPERT OPINION

Preclinical and clinical studies have shown promising evidence for palbociclib use in metastatic HER2+ and androgen receptor-expressing triple-negative breast cancer but mixed results in the adjuvant/neoadjuvant setting, where differences may only be detectable in high-risk disease. Palbociclib combinations may constitute viable replacements for chemotherapy in the neoadjuvant setting as part of de-escalation strategies. Investigation into synergy of palbociclib with immunotherapies is also ongoing based on non-canonical effects of CDK4/6 inhibition on the tumor immune microenvironment.

摘要

简介

激素受体阳性/HER2 阴性(HR+/HER2-)转移性乳腺癌患者从 CDK4/6 抑制剂帕博西利的治疗中获益,该抑制剂能够选择性地靶向细胞周期进展的机制,这些机制促进肿瘤细胞增殖。在这种情况下,与芳香酶抑制剂或氟维司群联合使用时,帕博西利的使用可改善无进展生存期。

涵盖领域

作者描述了帕博西利在乳腺癌中的研究现状,提供了支持帕博西利在其他类型转移性乳腺癌(如 HER2 阳性[HER2+]和三阴性)中发挥作用的证据,报告了正在进行的临床试验,旨在扩大帕博西利的使用范围,并讨论了预期的临床结果,这将更好地为包括帕博西利作为乳腺癌治疗策略的一部分的决策提供信息。

专家意见

临床前和临床研究表明,帕博西利在转移性 HER2+和雄激素受体表达的三阴性乳腺癌中具有有前途的应用证据,但在辅助/新辅助环境中的结果喜忧参半,在高危疾病中可能仅能检测到差异。帕博西利联合用药可能构成新辅助环境中化疗的可行替代品,作为降阶梯策略的一部分。基于 CDK4/6 抑制对肿瘤免疫微环境的非典型作用,正在对帕博西利与免疫疗法的协同作用进行研究。