Michelon Isabella, Castro Caio E R, Madeira Thiago, Dacoregio Maria Inez, Stecca Carlos, Soares Leonardo R, Saeed Anwaar, Vilbert Maysa, Cavalcante Ludimila
Department of Medicine, Catholic University of Pelotas, Pelotas, Brazil.
Department of Medicine, University of Brasilia, Brasilia, Brazil.
Cancer Treat Rev. 2025 Feb;133:102882. doi: 10.1016/j.ctrv.2025.102882. Epub 2025 Jan 6.
Trastuzumab deruxtecan (T-DXd) has shown promising activity in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and central nervous system (CNS) involvement. In this updated meta-analysis, we explore the effectiveness of T-DXd in a large subset of patients with HER2-positive BC and CNS disease.
A systematic search was made on September 16th, 2024, for studies investigating T-DXd in the scenario of HER2-positive BC and brain metastases (BMs) and/or leptomeningeal disease (LMD). We used random effects models for all statistical analyses.
We included 18 studies with 786 HER2-positive BC patients with CNS involvement (16 studies with 750 BMs patients and three studies with 36 LMD patients). We observed high overall antitumor responses (objective response rate [ORR], 60.4 %; disease control rate [DCR], 94.4 %; and clinical benefit rate [CBR], 79.3 %) and a 12-month PFS of 64.7 % and OS of 82.7 %. Intracranial ORR, DCR, and CBR were seen in 62.2 %, 88.6 %, and 68.6 % of patients, respectively, and 67.4 % achieved intracranial PFS at 12 months. Both stable and active BMs subgroups derived similar benefit from T-DXd. Better intracranial responses were seen for 33 patients with untreated BMs compared to 56 patients with previously treated or progressing lesions (odds ratio 3.82, 95 % confidence interval 1.3-10.8, p = 0.01). For the LMD group, T-DXd elicited intracranial ORR and CBR in 59.4 % and 94.1 % of patients, respectively.
This updated meta-analysis continues to support the overall and intracranial activity of T-DXd in patients with HER2-positive BC and CNS involvement, including those with LMD.
曲妥珠单抗德鲁昔单抗（T-DXd）在人类表皮生长因子受体2（HER2）阳性乳腺癌（BC）合并中枢神经系统（CNS）受累的患者中显示出有前景的活性。在这项更新的荟萃分析中，我们探讨T-DXd在大量HER2阳性BC合并CNS疾病患者中的有效性。
于2024年9月16日进行系统检索，以查找在HER2阳性BC和脑转移瘤（BMs）和/或软脑膜疾病（LMD）情况下研究T-DXd的研究。我们对所有统计分析使用随机效应模型。
我们纳入了18项研究，共786例HER2阳性BC合并CNS受累患者（16项研究有750例BMs患者，3项研究有36例LMD患者）。我们观察到较高的总体抗肿瘤反应（客观缓解率[ORR]为60.4%；疾病控制率[DCR]为94.4%；临床获益率[CBR]为79.3%），12个月无进展生存期（PFS）为64.7%，总生存期（OS）为82.7%。分别有62.2%、88.6%和68.6%的患者出现颅内ORR、DCR和CBR，67.4%的患者在12个月时实现颅内PFS。稳定和活跃的BMs亚组从T-DXd中获得的益处相似。与56例先前接受过治疗或病情进展的病变患者相比，33例未经治疗的BMs患者的颅内反应更好（优势比3.82，95%置信区间1.3 - 10.8，p = 0.01）。对于LMD组，T-DXd分别在59.4%和94.1%的患者中引发颅内ORR和CBR。
这项更新的荟萃分析继续支持T-DXd在HER2阳性BC合并CNS受累患者（包括LMD患者）中的总体和颅内活性。
