Results from a phase Ib study of trastuzumab emtansine (T-DM1), paclitaxel (T), and pertuzumab (P) in patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab.
Results from a phase Ib study of trastuzumab emtansine (T-DM1), paclitaxel (T), and pertuzumab (P) in patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab.
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曲妥珠单抗 emtansine (T-DM1)、紫杉醇 (T) 和帕妥珠单抗 (P) 在既往接受曲妥珠单抗治疗的 HER2 阳性转移性乳腺癌 (MBC) 患者中进行的 Ib 期研究结果。
DOI：
10.1200/jco.2012.30.15_suppl.528
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发表时间：
2012
影响因子：
45.3
通讯作者：
I. Krop
中科院分区：
文献类型：
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作者：
S. Modi;A. Elias;P. LoRusso;M. Samant;E. Guardino;B. Althaus;I. Krop
背景：抗体-药物偶联物T-DM 1在HER 2阳性MBC患者（pts）的II期研究中显示出单药活性。TDM 4652 g是一项Ib期、开放标签、剂量递增研究，评估T-DM 1（qw和q3 w）+ T（qw）± P（q3 w）在既往接受过曲妥珠单抗治疗的HER 2阳性MBC患者中的安全性和耐受性。对于T-DM 1 + T，使用3+3剂量递增方案以确定最大耐受剂量（MTD）;在该MTD下添加P。修改了初始限制性剂量限制性毒性（DLT）标准，以确定更具临床相关性的MTD。结果：我们报告了使用改良DLT标准的T-DM 1（qw和q3 w）+ T（+ P）的中期结果。这些队列入组了24例患者;中位年龄为53岁（范围：23-69）*; MBC中既往全身治疗的中位次数为7次（范围：2-15）*。见下表。结论：联合应用T-DM 1 + T ± P治疗的MTD值可作为临床治疗的参考。
528 Background: The antibody–drug conjugate T-DM1 has shown single-agent activity in phase II studies in patients (pts) with HER2–positive MBC. Preclinical data suggest synergy for T-DM1 combined with taxanes and with P. Methods: TDM4652g is a phase Ib, open-label, dose-escalation study evaluating the safety and tolerability of T-DM1 (qw and q3w) + T (qw) ± P (q3w) in pts with HER2-positive MBC previously treated with trastuzumab. A 3+3 dose-escalation scheme is used for T-DM1 + T to determine the maximum tolerated dose (MTD); P is added at this MTD. Initial restrictive dose-limiting toxicity (DLT) criteria were modified to establish a more clinically relevant MTD. Results: We report interim results with T-DM1 (qw and q3w) + T (+ P) using modified DLT criteria. 24 pts have been enrolled in these cohorts; median age was 53 yrs (range, 23–69)*; median number of prior systemic therapies in MBC was 7 (range, 2–15)*. See table below. Conclusions: Data support combining T-DM1 + T ± P at the MTD for future clini...