Department of Neurological Surgery & Brain Metastasis Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Department of Neurological Surgery, Weill Cornell Medicine, New York, NY 10065, USA.
CNS Oncol. 2022 Sep 1;11(3):CNS90. doi: 10.2217/cns-2022-0010. Epub 2022 Jun 8.
Antibody-drug conjugates have transformed the treatment of HER2+ breast and other cancers. Unfortunately, the CNS remains a sanctuary site for many such patients in part due to poor macromolecule penetration across the blood-brain tumor barrier. Trastuzumab deruxtecan (T-DXd), a high-payload antibody-drug conjugate, was recently found to improve progression-free survival in HER2+ breast cancer patients versus prior-generation trastuzumab emtansine, prompting us to evaluate CNS activity in a woman with brain-only metastatic disease. T-DXd achieved complete response despite heavy pretreatment. Three persistent, previously-irradiated lesions were biopsy-proven to represent treatment effect. Subsequent recurrence occurred upon treatment holiday; partial response was observed with rechallenge. This case suggests T-DXd is active in HER2+ breast cancer brain metastases and supports further prospective evaluation.
抗体偶联药物已经改变了 HER2+ 乳腺癌和其他癌症的治疗方法。不幸的是，由于大分子穿过血脑肿瘤屏障的能力较差，许多此类患者的中枢神经系统仍然是避难所。曲妥珠单抗 deruxtecan（T-DXd）是一种高载量抗体药物偶联物，最近被发现可改善 HER2+乳腺癌患者的无进展生存期，优于前一代曲妥珠单抗emtansine，促使我们在一名仅有脑转移疾病的女性中评估中枢神经系统的活性。尽管预处理量大，T-DXd 仍达到完全缓解。三个持续存在的、先前接受过放疗的病变经活检证实代表治疗效果。治疗中断后发生了随后的复发；重新治疗时观察到部分缓解。该病例表明 T-DXd 在 HER2+乳腺癌脑转移中具有活性，并支持进一步的前瞻性评估。
