Martínez María Teresa, Pérez-Fidalgo José Alejandro, Martín-Martorell Paloma, Cejalvo Juan Miguel, Pons Vanesa, Bermejo Begoña, Martín Miguel, Albanell Joan, Lluch Ana
Dept. of Hematology and Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, "Rio Hortega Project in research training" (CM12/00264), Spain.
Dept. of Hematology and Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Spain.
Crit Rev Oncol Hematol. 2016 Jan;97:96-106. doi: 10.1016/j.critrevonc.2015.08.011. Epub 2015 Aug 11.
Trastuzumab emtansine (T-DM1), a new agent developed for the treatment of HER2-positive breast cancer, is an antibody-drug conjugate with a complex compound obtained by the conjugation of trastuzumab, a stable thioether linker, and the potent cytotoxic drug maytansine-derivate(DM1), which inhibits cell division and induces cell death.
PubMed database, ESMO, ASCO, San Antonio Breast Cancer Symposium Meeting abstracts and clinicaltrials.gov were searched using the terms "Anti-HER2 treatment breast cancer and trastuzumab emtansine (T-DM1) "; papers considered relevant for the aim of this review were selected.
FINDINGS/RESULTS: The phase I trials have determined the safe dosing range of T-DM1, established at 3.6 mg/kg every 3 weeks. The phase III randomized EMILIA and TR3RESA trials have shown that T-DM1 provides objective tumor responses and significantly improves progression free survival and overall survival in HER2-positive metastatic breast cancer patients previously treated with anti-HER2-based regimens. The ongoing phase III trials KAITLIN and KATHERINE will give us further information about the place T-DM1 should occupy in the treatment of patients with early stage HER2-positive breast cancer. In this review we analyze the most relevant clinical trials conducted with T-DM1 and the role of this compound in the management of advanced breast cancer.
T-DM1 has shown clinically relevant activity in the treatment of HER2-positive breast cancer patients after progression on trastuzumab and taxane based therapy, both in the second line treatment setting and after early relapse on adjuvant trastuzumab therapy. This is accompanied by a favorable safety and tolerability profile.
曲妥珠单抗-美坦新偶联物（T-DM1）是一种开发用于治疗HER2阳性乳腺癌的新型药物，它是一种抗体药物偶联物，由曲妥珠单抗、稳定的硫醚连接子和强效细胞毒性药物美坦新衍生物（DM1）偶联而成的复合化合物，可抑制细胞分裂并诱导细胞死亡。
使用“抗HER2治疗乳腺癌和曲妥珠单抗-美坦新偶联物（T-DM1）”检索了PubMed数据库、欧洲肿瘤内科学会（ESMO）、美国临床肿瘤学会（ASCO）、圣安东尼奥乳腺癌研讨会会议摘要以及美国国立医学图书馆临床试验注册库（clinicaltrials.gov）；选择了与本综述目的相关的论文。
I期试验确定了T-DM1的安全给药范围，为每3周3.6mg/kg。III期随机EMILIA和TR3RESA试验表明，T-DM1可提供客观的肿瘤反应，并显著改善先前接受基于抗HER2方案治疗的HER2阳性转移性乳腺癌患者的无进展生存期和总生存期。正在进行的III期试验KAITLIN和KATHERINE将为我们提供关于T-DM1在早期HER2阳性乳腺癌患者治疗中应占据的地位的更多信息。在本综述中，我们分析了使用T-DM1进行的最相关临床试验以及该化合物在晚期乳腺癌管理中的作用。
T-DM1在曲妥珠单抗和紫杉烷类治疗进展后的HER2阳性乳腺癌患者的二线治疗以及辅助曲妥珠单抗治疗早期复发后的治疗中均显示出临床相关活性。同时，它具有良好的安全性和耐受性。
