Division of Neuro-Oncology, Department of Neurology and Neurological Sciences, Stanford Medicine, Stanford, CA, 94305, USA.
J Neurooncol. 2024 Oct;170(1):209-217. doi: 10.1007/s11060-024-04788-y. Epub 2024 Jul 29.
Emerging data suggest that trastuzumab deruxtecan (T-DXd) is an active treatment for brain metastases from HER2 + breast cancer. We aimed to characterize the activity of T-DXd in the treatment of leptomeningeal metastases (LM) from a range of HER2-altered cancers.
We reviewed neuro-oncology clinic records between July 2020 and December 2023 to identify patients who received T-DXd to treat LM.
Of 18 patients identified, 6 had HER2 + breast cancer, 8 had HER2-low/negative breast cancer, 2 had HER2 + gastroesophageal cancer, and 2 had HER2-mutant non-small cell lung cancer (NSCLC). 10/18 (56%) patients had cytologically confirmed LM by CSF cytology or circulating tumor cell (CTC) capture. A partial response (PR) on MRI using the EORTC/RANO-LM Revised-Scorecard occurred in 4/6 (67%) patients with HER2 + breast LM, 2/8 (25%) patients with HER2-low/negative breast cancer, and 0/4 (0%) patients with HER2 + gastroesophageal cancer or HER2-mutant NSCLC. Median overall survival after initiating T-DXd was 5.8 months. Survival after initiating T-DXd was numerically longer for HER2 + breast cancer patients compared with HER2-low/negative breast and HER2-altered non-breast cancer patients (13.9 months vs. 5.2 months and 4.6 months, respectively). Landmark analysis showed that patients with radiologic LM response to T-DXd by 2.5 months had longer survival than non-responders (14.2 months vs. 2.6 months, HR 0.18, 95% CI 0.05-0.63, p < 0.05), and landmark analyses at 3.5 and 4.5 months after starting T-DXd showed a similar but nonsignificant trend.
T-DXd induces LM responses in a subset of patients, and such responses may be associated with prolongation of survival. Prospective trials are needed to clarify the role of T-DXd in treating LM and which patients are most likely to benefit.
新出现的数据表明，曲妥珠单抗-德鲁替康（T-DXd）是治疗 HER2 阳性乳腺癌脑转移的有效治疗方法。我们旨在描述 T-DXd 治疗一系列 HER2 改变的癌症所致脑膜转移（LM）的活性。
我们回顾了 2020 年 7 月至 2023 年 12 月间神经肿瘤学临床记录，以确定接受 T-DXd 治疗 LM 的患者。
在确定的 18 名患者中，6 名患有 HER2 阳性乳腺癌，8 名患有 HER2 低/阴性乳腺癌，2 名患有 HER2 阳性胃食管癌，2 名患有 HER2 突变型非小细胞肺癌（NSCLC）。10/18（56%）名患者通过 CSF 细胞学或循环肿瘤细胞（CTC）捕获确认 LM 细胞学阳性。6 名 HER2 阳性乳腺癌 LM 患者中，4 名（67%）MRI 采用 EORTC/RANO-LM 修订评分卡评估出现部分缓解（PR），8 名 HER2 低/阴性乳腺癌患者中 2 名（25%）出现 PR，4 名 HER2 阳性胃食管癌患者或 2 名 HER2 突变型 NSCLC 患者中无 1 名出现 PR。T-DXd 起始后中位总生存期为 5.8 个月。与 HER2 低/阴性乳腺癌和 HER2 改变的非乳腺癌患者相比，HER2 阳性乳腺癌患者 T-DXd 起始后的生存时间更长（分别为 13.9 个月、5.2 个月和 4.6 个月）。生存分析表明，T-DXd 治疗 2.5 个月时 MRI 显示有 LM 反应的患者比无反应的患者生存期更长（14.2 个月比 2.6 个月，HR 0.18，95%CI 0.05-0.63，p<0.05），T-DXd 起始后 3.5 个月和 4.5 个月的生存分析也显示出类似但无统计学意义的趋势。
T-DXd 在一部分患者中诱导 LM 反应，此类反应可能与生存期延长有关。需要前瞻性试验来明确 T-DXd 在治疗 LM 中的作用以及哪些患者最有可能受益。
