Trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer and brain metastases: exploratory final analysis of cohort 1 from KAMILLA, a single-arm phase IIIb clinical trial☆.

文献信息

DOI	10.1016/j.annonc.2020.06.020
PMID	32634611
期刊	Annals of oncology : official journal of the European Society for Medical Oncology
影响因子	65.4
JCR 分区	Q1
发表年份	2020
被引次数	188
关键词	HER2阳性乳腺癌，KAMILLA，T-DM1，脑转移，转移性乳腺癌
文献类型	Clinical Trial, Phase III, Journal Article, Research Support, Non-U.S. Gov't
ISSN	0923-7534
页码	1350-1358
期号	31(10)
作者	F Montemurro, S Delaloge, C H Barrios, R Wuerstlein, A Anton, E Brain, T Hatschek, C M Kelly, C Peña-Murillo, M Yilmaz, M Donica, P Ellis

一句话小结

本研究评估了曲妥珠单抗艾美替尼（T-DM1）在HER2阳性乳腺癌伴脑转移患者中的疗效，结果显示在126名可测量脑转移患者中最佳总体反应率为21.4%，临床获益率为42.9%，中位无进展生存期为5.5个月，中位总体生存期为18.9个月，且T-DM1耐受性良好。这一发现为治疗这一难治人群提供了新的可能性，值得进一步研究。

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HER2阳性乳腺癌 · KAMILLA · T-DM1 · 脑转移 · 转移性乳腺癌

摘要

背景
来自人类表皮生长因子受体2（HER2）阳性乳腺癌的脑转移（BM）患者是一个难以治疗的人群。曲妥珠单抗艾美替尼（T-DM1）在这部分患者中在小规模临床系列中显示出潜在的疗效。

患者和方法
KAMILLA是一项正在进行的IIIb期研究，旨在评估在接受过HER2靶向治疗和化疗的HER2阳性局部晚期/转移性乳腺癌患者中使用T-DM1。患者每3周静脉注射T-DM1 3.6 mg/kg，直至出现不可接受的毒性、撤回同意或疾病进展。在此后分析中，评估了基线BM患者的肿瘤反应和临床结果。主要终点指标为最佳总体反应率（完全反应+部分反应）和临床获益率（完全反应+部分反应+持续≥6个月的稳定病），均采用RECIST v1.1标准进行评估，此外还包括无进展生存期、总体生存期和安全性。

结果
在2002名接受治疗的患者中，398名患者存在基线BM。在126名可测量BM的患者中，最佳总体反应率和临床获益率分别为21.4%（95%可信区间[CI] 14.6-29.6）和42.9%（95% CI 34.1-52.0）。BM主径和的总和减少≥30%发生在42.9%（95% CI 34.1-52.0）患者中，包括在67名未接受过BM放疗的患者中，发生率为49.3%（95% CI 36.9-61.8）。在398名基线BM患者中，中位无进展生存期和中位总体生存期分别为5.5个月（95% CI 5.3-5.6）和18.9个月（95% CI 17.1-21.3）。不良事件的发生情况在基线BM患者与非基线BM患者之间大致相似，尽管神经系统不良事件在基线BM患者中更为常见[208例（52.3%）]，而在非基线BM患者中则为[701例（43.7%）]。

结论
这项对参与前瞻性临床试验的HER2阳性转移性乳腺癌伴BM患者的探索性分析表明，T-DM1在这一人群中具有活性且耐受性良好。应进一步探索T-DM1在该环境中的应用。

试验注册
ClinicalTrials.gov识别码：NCT01702571。

英文摘要

BACKGROUND Patients with brain metastases (BM) from human epidermal growth factor receptor 2 (HER2)-positive breast cancer represent a difficult-to-treat population. Trastuzumab emtansine (T-DM1) has shown potential activity in this subset of patients in small clinical series.

PATIENTS AND METHODS KAMILLA is an ongoing, phase IIIb study of T-DM1 in patients with HER2-positive locally advanced/metastatic breast cancer with prior HER2-targeted therapy and chemotherapy. Patients received T-DM1 3.6 mg/kg every 3 weeks (intravenously) until unacceptable toxicity, withdrawal of consent, or disease progression. Tumor response and clinical outcomes in patients with baseline BM were evaluated in this post hoc, exploratory analysis. The main outcome measures were best overall response rate (complete response + partial response) and clinical benefit rate (complete response + partial response + stable disease lasting ≥6 months) by RECIST v1.1 criteria, progression-free survival, overall survival, and safety.

RESULTS Of 2002 treated patients, 398 had baseline BM. In 126 patients with measurable BM, the best overall response rate and clinical benefit rate were 21.4% [95% confidence interval (CI) 14.6-29.6] and 42.9% (95% CI 34.1-52.0), respectively. A reduction in the sum of the major diameters of BM ≥30% occurred in 42.9% (95% CI 34.1-52.0), including 49.3% (95% CI 36.9-61.8) of 67 patients without prior radiotherapy to BM. In the 398 patients with baseline BM, median progression-free survival and overall survival were 5.5 (95% CI 5.3-5.6) months and 18.9 (95% CI 17.1-21.3) months, respectively. The adverse event profile was broadly similar in patients with and without baseline BM, although nervous system adverse events were more common in patients with [208 (52.3%)] versus without [701 (43.7%)] baseline BM.

CONCLUSION This exploratory analysis of patients with HER2-positive metastatic breast cancer and BM enrolled in a prospective clinical trial shows that T-DM1 is active and well-tolerated in this population. T-DM1 should be explored further in this setting.

TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01702571.

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主要研究问题

核心洞察

研究背景和目的
HER2阳性乳腺癌患者在脑转移（BM）发生后，常常面临治疗困难。Trastuzumab emtansine（T-DM1）作为一种靶向药物，已在小规模临床研究中显示出对这一特殊人群的潜在疗效。本研究的目的是在KAMILLA这项单臂IIIb期临床试验中，探索T-DM1在接受过HER2靶向治疗和化疗的HER2阳性转移性乳腺癌患者（包括脑转移患者）的有效性与安全性。
主要方法和发现
在2002名接受T-DM1治疗的患者中，有398名患者在基线时存在脑转移。在126名具有可测量脑转移的患者中，最佳总体反应率（包括完全反应和部分反应）为21.4%（95%置信区间[CI]：14.6-29.6），而临床获益率（包括完全反应、部分反应和持续≥6个月的稳定病情）则为42.9%（95% CI：34.1-52.0）。42.9%的患者（95% CI：34.1-52.0）在脑转移的最大直径总和减少≥30%，其中67名没有接受过放疗的患者中有49.3%（95% CI：36.9-61.8）。对于398名基线存在脑转移的患者，中位无进展生存期（PFS）为5.5个月（95% CI：5.3-5.6），中位生存期（OS）为18.9个月（95% CI：17.1-21.3）。同时，患有脑转移的患者与没有脑转移的患者在不良事件方面的表现相似，但神经系统不良事件在有脑转移患者中更为常见（52.3% vs 43.7%）。
核心结论
本次探索性分析表明，T-DM1在HER2阳性转移性乳腺癌伴脑转移的患者中展现了良好的疗效和耐受性，提示其在该特定人群中具有治疗潜力。
研究意义和影响
本研究为HER2阳性转移性乳腺癌伴脑转移的治疗提供了新的视角，证实了T-DM1作为一种有效治疗选择的潜力，推动了对该人群进一步研究的必要性。这一发现不仅为临床实践提供了依据，还可能影响未来的治疗指南，改善这一难治患者群体的治疗预后。

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... (178 更多篇文献)

Trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer and brain metastases: exploratory final analysis of cohort 1 from KAMILLA, a single-arm phase IIIb clinical trial☆. ​

文献信息 ​

一句话小结 ​

在麦伴科研 (maltsci.com) 搜索更多文献 ​

摘要 ​

英文摘要 ​

麦伴智能科研服务 ​

主要研究问题 ​

核心洞察 ​

引用本文的文献 ​