A Pooled Analysis of Trastuzumab Deruxtecan in Patients With HER2-Positive Metastatic Breast Cancer With Brain Metastases.

IF 56.7 1区医学 Q1 ONCOLOGY

Annals of Oncology Pub Date : 2024-09-04 DOI:10.1016/j.annonc.2024.08.2347

F André, J Cortés, G Curigliano, S Modi, W Li, Y H Park, W-P Chung, S-B Kim, T Yamashita, J L Pedrini, S-A Im, L-M Tseng, N Harbeck, I Krop, S Nakatani, K Tecson, S Ashfaque, A Egorov, S A Hurvitz

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引用次数: 0

Abstract

Background: This exploratory pooled analysis investigated the efficacy and safety of trastuzumab deruxtecan (T-DXd) versus comparator treatment in patients with HER2-positive metastatic breast cancer (mBC) with brain metastases (BMs) at baseline, categorized according to previous local treatment.

Patients and methods: T-DXd data were pooled from DESTINY-Breast01/-02/-03. Comparator data, from patients receiving physician's choice therapy and trastuzumab emtansine, were pooled from DESTINY-Breast02 and -03, respectively. Baseline BM status was assessed according to US Food and Drug Administration criteria. Endpoints included intracranial objective response rate (ORR; complete or partial response in brain) per blinded independent central review (BICR) by RECIST v1.1, time to intracranial response, intracranial duration of response (DoR), central nervous system progression-free survival (CNS-PFS) by BICR, overall survival (OS), and safety.

Results: 148 patients who received T-DXd and 83 patients who received comparator treatment had BMs at baseline. In those who were treated with T-DXd, the intracranial ORR of patients with treated/stable and untreated/active BMs was 45.2% and 45.5%, respectively. The median (range) time to intracranial response was 2.8 months (1.1-13.9 months) and 1.5 months (1.2-13.7 months) in patients with treated/stable and untreated/active BMs, respectively. For those with treated/stable BMs, the median (95% CI) intracranial DoR was 12.3 months (9.1-17.9 months), and for those with untreated/active BMs it was 17.5 months (13.6-31.6 months). The median (95% CI) CNS-PFS and OS was 12.3 months (11.1-13.8 months) and not reached (22.1 months-not estimable [NE]) in those with treated/stable BMs, and 18.5 months (13.6-23.3 months) and 30.2 months (21.3 months-NE) in those with untreated/active BMs, respectively. Drug-related TEAEs grade ≥3 were experienced by 43.2% of patients with BMs and 46.4% without BMs with T-DXd.

Conclusions: T-DXd demonstrated meaningful intracranial efficacy and clinical benefit in OS, with an acceptable and manageable safety profile in patients with HER2-positive mBC with treated/stable and untreated/active BMs.

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曲妥珠单抗德鲁司坦治疗HER2阳性转移性乳腺癌脑转移患者的汇总分析

研究背景这项探索性汇总分析研究了曲妥珠单抗德鲁司坦（T-DXd）与对比治疗的疗效和安全性，研究对象为基线时有脑转移（BMs）的HER2阳性转移性乳腺癌（mBC）患者，根据既往的局部治疗进行分类：T-DXd数据汇集自DESTINY-Breast01/-02/-03。对照组数据来自接受医生选择疗法和曲妥珠单抗的患者，分别来自DESTINY-Breast02和-03。基线BM状态根据美国食品药品管理局的标准进行评估。终点包括RECIST v1.1标准的颅内客观反应率（ORR；脑部完全或部分反应）、颅内反应时间、颅内反应持续时间（DoR）、BICR标准的中枢神经系统无进展生存期（CNS-PFS）、总生存期（OS）和安全性：148名接受T-DXd治疗的患者和83名接受对比治疗的患者基线时有BMs。在接受T-DXd治疗的患者中，治疗/稳定和未治疗/活动性BMs患者的颅内ORR分别为45.2%和45.5%。颅内反应时间的中位数（范围）分别为2.8个月（1.1-13.9个月）和1.5个月（1.2-13.7个月）。对于接受治疗/病情稳定的骨髓瘤患者，颅内DoR的中位数（95% CI）为12.3个月（9.1-17.9个月），而对于未接受治疗/病情活跃的骨髓瘤患者，颅内DoR的中位数（95% CI）为17.5个月（13.6-31.6个月）。中位数（95% CI）CNS-PFS和OS在接受治疗/病情稳定的BMs患者中分别为12.3个月（11.1-13.8个月）和未达到（22.1个月-无法估计[NE]），在未接受治疗/病情活跃的BMs患者中分别为18.5个月（13.6-23.3个月）和30.2个月（21.3个月-NE）。服用T-DXd后，43.2%的BMs患者和46.4%的无BMs患者出现了≥3级的药物相关TEAEs：结论：T-DXd对HER2阳性、伴有治疗/稳定和未治疗/活动性BMs的mBC患者具有显著的颅内疗效和OS临床获益，同时具有可接受、可管理的安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Oncology 医学-肿瘤学

CiteScore

63.90

自引率

1.00%

发文量

3712

审稿时长

2-3 weeks

期刊介绍： Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine. The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings. Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.

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