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中华乳腺病杂志(电子版) ›› 2022, Vol. 16 ›› Issue (02) : 110 -115. doi: 10.3877/cma.j.issn.1674-0807.2022.02.008

综述

细胞周期蛋白依赖性激酶4/6抑制剂在乳腺癌治疗中的新策略
张军1, 赵崇如1, 刘万立1, 刘强2,()   
  1. 1. 518000 广东省深圳市前海蛇口自贸区医院甲状腺乳腺外科
    2. 510000 广州,中山大学孙逸仙纪念医院乳腺外科
  • 收稿日期:2021-11-22 出版日期:2022-04-01
  • 通信作者: 刘强

New strategy for cyclin­dependent kinase 4/6 inhibitors in breast cancer treatment

Jun Zhang1, Chongru Zhao1, Wanli Liu1   

  • Received:2021-11-22 Published:2022-04-01
引用本文:

张军, 赵崇如, 刘万立, 刘强. 细胞周期蛋白依赖性激酶4/6抑制剂在乳腺癌治疗中的新策略[J]. 中华乳腺病杂志(电子版), 2022, 16(02): 110-115.

Jun Zhang, Chongru Zhao, Wanli Liu. New strategy for cyclin­dependent kinase 4/6 inhibitors in breast cancer treatment[J]. Chinese Journal of Breast Disease(Electronic Edition), 2022, 16(02): 110-115.

细胞周期蛋白依赖性激酶(CDK)4/6是细胞进入S期的关键因子,在包括乳腺癌在内的多种类型肿瘤的生长中起着重要作用。随着CDK4/6抑制剂药物的问世,其联合内分泌治疗已逐步成为激素受体(HR)阳性、HER-2阴性的局部晚期以及转移性乳腺癌患者的标准一线治疗手段。近年来,CDK4/6抑制剂的临床适应证在文献报道中不断扩展,笔者就CDK4/6信号通路失调的致癌机制及CDK4/6抑制剂在乳腺癌治疗中的应用进行综述。

表1 CDK4/6抑制剂联合AI用于初治HR阳性、HER-2阴性晚期乳腺癌的3期临床研究
表2 CDK4/6抑制剂联合氟维司群用于内分泌治疗进展的HR阳性、HER-2阴性晚期乳腺癌的3期临床研究
表3 CDK4/6抑制剂联合内分泌治疗用于HR阳性、HER-2阴性早期乳腺癌的3期临床研究
表4 目前正在进行的CDK4/6抑制剂治疗乳腺癌3期临床研究
研究名称 研究注册号 入组患者 用药方案 主要终点 次要终点
SONIA[59] NCT03425838 一线或二线HR阳性晚期乳腺癌 一线CDK4/6抑制剂联合NSAI、二线氟维司群比一线NSAI、二线氟维司群联合CDK4/6抑制剂 二线治疗的PFS 总生存、安全性、生活质量、药物经济学、缓解率、生物标记物
SAFIA[60] NCT03447132 氟维司群治疗后可手术的luminal型乳腺癌新辅助治疗 氟维司群联合palbociclib比氟维司群 根据Le Chevalier分类的pCR 根据Sataloff分类的pCR、放射影像学缓解率、保留乳房率、安全性、无疾病生存和总生存
POLAR[61] NCT03820830 HR阳性、HER-2阴性乳腺癌孤立局部复发 palbociclib联合标准内分泌治疗比标准内分泌治疗 无侵袭性疾病生存期 安全性、无乳腺癌间期、无远处复发间期、总生存
POETIC-A[62] NCT04584853 术前AI治疗2周后通过高Ki67确定5年复发风险高的绝经后原发性乳腺癌 abemaciclib联合内分泌治疗比内分泌治疗 复发时间 无复发生存、至远处复发时间、乳腺癌相关生存、总生存、患者生活质量、治疗相关死亡
NATALEE[63] NCT03701334 HR阳性、HER-2阴性早期乳腺癌 ribociclib联合内分泌治疗比内分泌治疗 无侵袭性疾病生存期 无复发生存、无远处复发疾病生存、总生存、生活质量、ribociclib的药物代谢动力学参数
CHEVENDO[64] NCT02344472 HR阳性、HER-2阳性晚期乳腺癌 曲妥珠单克隆抗体、帕妥珠单克隆抗体联合化疗后双靶联合ribociclib+内分泌治疗维持比曲妥珠单克隆抗体、帕妥珠单克隆抗体联合ribociclib+内分泌治疗 发生不良事件的例数 总缓解率、安全性、生存质量、生物标记物、疾病控制率、无进展生存、总生存
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