DESTINY-Breast03 是一项针对人表皮生长因子受体 2 (HER2) 阳性转移性乳腺癌患者的曲妥珠单抗 deruxtecan (T-DXd) 与曲妥珠单抗 emtansine (T-DM1) 的随机、多中心、开放标签 III 期研究。 mBC）之前曾接受过曲妥珠单抗和紫杉烷治疗。初步分析显示，与 T-DM1 相比，无进展生存期 (PFS) 有统计学显着改善。在这里，我们报告了基线时患有和不患有脑转移 (BM) 的患者的探索性疗效数据。患者以 1:1 的比例随机分配接受 T-DXd 5.4 mg/kg 或 T-DM1 3.6 mg/kg。临床上不活动/无症状 BM 的患者符合资格。根据修订版 RECIST 1.1 版测量病变。结果包括盲法独立中心审查 (BICR) 的 PFS、客观缓解率 (ORR) 以及根据 BICR 的颅内 ORR。 截至 2021 年 5 月 21 日，43/261 名患者随机分配至 T-DXd，39/263 名患者随机分配至 T-根据研究者评估，DM1 在基线时具有 BM。在具有基线 BM 的患者中，T-DXd 组中 20/43 的患者和 T-DM1 组中 19/39 的患者之前未接受过局部 BM 治疗。对于患有 BM 的患者，T-DXd 的中位 PFS 为 15.0 个月 [95% 置信区间 (CI) 12.5-22.2 个月]，而 T-DM1 为 3.0 个月（95% CI 2.8-5.8 个月）；风险比 (HR) 0.25 (95% CI 0.13-0.45)。对于没有 BM 的患者，T-DXd 未达到中位 PFS（95% CI 22.4 个月 - 不可估计），而 T-DM1 为 7.1 个月（95% CI 5.6-9.7 个月）； HR 0.30（95% CI 0.22-0.40）。对于有和没有 BM 的患者，经确认的全身 ORR 分别为：T-DXd 为 67.4%，T-DM1 为 20.5%；T-DXd 为 82.1%，T-DM1 为 36.6%。 T-DXd 组的颅内 ORR 为 65.7%，而 T-DM1 组为 34.3%。 与 T-DM1 相比，接受曲妥珠单抗和紫杉烷治疗后疾病进展的 HER2 阳性 mBC 患者从 T-DXd 治疗中获得了显着的获益，包括患有以下疾病的患者：基线 BMs.版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

DESTINY-Breast03 is a randomized, multicenter, open-label, phase III study of trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab and a taxane. A statistically significant improvement in progression-free survival (PFS) versus T-DM1 was reported in the primary analysis. Here, we report exploratory efficacy data in patients with and without brain metastases (BMs) at baseline.Patients were randomly assigned 1 : 1 to receive T-DXd 5.4 mg/kg or T-DM1 3.6 mg/kg. Patients with clinically inactive/asymptomatic BMs were eligible. Lesions were measured as per modified RECIST, version 1.1. Outcomes included PFS by blinded independent central review (BICR), objective response rate (ORR), and intracranial ORR as per BICR.As of 21 May 2021, 43/261 patients randomized to T-DXd and 39/263 patients randomized to T-DM1 had BMs at baseline, as per investigator assessment. Among patients with baseline BMs, 20/43 in the T-DXd arm and 19/39 in the T-DM1 arm had not received prior local BM treatment. For patients with BMs, median PFS was 15.0 months [95% confidence interval (CI) 12.5-22.2 months] for T-DXd versus 3.0 months (95% CI 2.8-5.8 months) for T-DM1; hazard ratio (HR) 0.25 (95% CI 0.13-0.45). For patients without BMs, median PFS was not reached (95% CI 22.4 months-not estimable) for T-DXd versus 7.1 months (95% CI 5.6-9.7 months) for T-DM1; HR 0.30 (95% CI 0.22-0.40). Confirmed systemic ORR was 67.4% for T-DXd versus 20.5% for T-DM1 and 82.1% for T-DXd versus 36.6% for T-DM1 for patients with and without BMs, respectively. Intracranial ORR was 65.7% with T-DXd versus 34.3% with T-DM1.Patients with HER2-positive mBC whose disease progressed after trastuzumab and a taxane achieved a substantial benefit from treatment with T-DXd compared with T-DM1, including those with baseline BMs.Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.