Sachdev Jasgit C, Jahanzeb Mohammad
Virginia G. Piper Cancer Center Clinical Trials, HonorHealth Research Institute and Translational Genomics Research Institute, Scottsdale, AZ.
Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Deerfield Beach, FL.
Clin Breast Cancer. 2016 Apr;16(2):73-81. doi: 10.1016/j.clbc.2015.09.007. Epub 2015 Sep 25.
Agents that target microtubule (MT) dynamics have been used extensively for the treatment of metastatic breast cancer (MBC). Among these agents are taxanes (solvent-based paclitaxel [sb-paclitaxel], docetaxel, and nab-paclitaxel) and non-taxanes, such as eribulin and ixabepilone. Although these agents have been approved for the treatment of MBC, questions regarding the ideal agent, regimen (single agent vs. combination vs. sequential), and schedule still remain. This systematic review examined pivotal trials for taxanes, eribulin, and ixabepilone as well as first-line taxane trials in MBC. Only randomized trials that enrolled ≥ 100 patients were included. Publications on combination regimens with targeted agents were excluded unless they also included a comparison between nontargeted regimens. The studies were grouped into taxane versus taxane, sb-paclitaxel versus non-taxane, and docetaxel versus non-taxane regimens. In taxane versus taxane comparisons, the efficacy of sb-paclitaxel and docetaxel appeared similar, nab-paclitaxel every 3 weeks (q3w) appeared superior to sb-paclitaxel q3w, and weekly nab-paclitaxel appeared superior to docetaxel. In general, taxane regimens demonstrated higher overall response rates (ORRs) versus non-taxane regimens; however, only 2 trials demonstrated longer overall survival (OS) for taxane regimens. Taxanes will likely continue to be used in earlier lines of therapy, whereas eribulin and ixabepilone may be more appropriate for later lines of treatment. Ongoing research may identify biomarkers that could help in selecting the appropriate MT-targeted agent for a given patient.
靶向微管(MT)动力学的药物已被广泛用于治疗转移性乳腺癌(MBC)。这些药物包括紫杉烷类(溶剂型紫杉醇[sb-紫杉醇]、多西他赛和纳米白蛋白结合型紫杉醇)和非紫杉烷类,如艾日布林和伊沙匹隆。尽管这些药物已被批准用于治疗MBC,但关于理想药物、治疗方案(单药治疗与联合治疗与序贯治疗)以及给药方案的问题仍然存在。本系统评价研究了紫杉烷类、艾日布林和伊沙匹隆的关键试验以及MBC的一线紫杉烷类试验。仅纳入了入组≥100例患者的随机试验。排除了有关靶向药物联合治疗方案的出版物,除非它们还包括非靶向治疗方案之间的比较。这些研究被分为紫杉烷类与紫杉烷类、sb-紫杉醇与非紫杉烷类以及多西他赛与非紫杉烷类治疗方案。在紫杉烷类与紫杉烷类的比较中,sb-紫杉醇和多西他赛的疗效似乎相似,纳米白蛋白结合型紫杉醇每3周(q3w)给药似乎优于sb-紫杉醇q3w,纳米白蛋白结合型紫杉醇每周给药似乎优于多西他赛。一般来说,紫杉烷类治疗方案的总体缓解率(ORR)高于非紫杉烷类治疗方案;然而,只有2项试验显示紫杉烷类治疗方案的总生存期(OS)更长。紫杉烷类可能会继续用于早期治疗,而艾日布林和伊沙匹隆可能更适合晚期治疗。正在进行的研究可能会确定有助于为特定患者选择合适的MT靶向药物的生物标志物。