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