抗体-药物缀合物(ADC)代表实体瘤和血液肿瘤的系统治疗中的革命性方法。由抗体构成,细胞毒性有效载荷,和一个链接器,ADC旨在选择性地将细胞毒性剂递送至肿瘤,同时保留正常组织。到目前为止,已经测试并批准了多种ADC用于多种实体瘤,但是如果有一个对临床实践有重大影响,这就是曲妥珠单抗-deruxtecan(T-DXd).值得注意的是,T-DXd被批准用于HER2阳性和HER2低转移性乳腺癌(MBC),HER2阳性胃癌(GC),HER2突变型非小细胞肺癌(NSCLC)和HER23+实体瘤。此外,它接受了HER2阳性结直肠癌(CRC)的突破性治疗.
■我们回顾了T-DXd的临床前和临床数据,重点是正在进行的早期试验,探索联合疗法以增强表达HER2的实体瘤中T-DXd的活性。
■T-DXd的临床使用仍然引起患者选择的问题,治疗持续时间,优先于其他批准的ADC,和管理抵抗。对T-DXd毒性的担忧仍然存在,特别是涉及潜在毒性药物的组合。生物标志物识别和联合疗法的进步为提高疗效和克服对T-DXd的耐药性提供了有希望的途径。最终改善癌症患者的预后。
UNASSIGNED: Antibody-drug conjugates (ADCs) represent a revolutionary approach in the systemic treatment for both solid and hematologic tumors. Constituted by an antibody, a cytotoxic payload, and a linker, ADCs aim to selectively deliver cytotoxic agents to tumors while sparing normal tissues. Various ADCs have been tested and approved for multiple solid tumors so far, but if there is one that had a major impact on clinical practice, this is Trastuzumab-deruxtecan (T-DXd). Notably, T-DXd was approved for HER2-positive and HER2-low metastatic breast cancer (MBC), HER2-positive gastric cancer (GC), HER2-mutant non-small cell lung cancer (NSCLC) and HER2 3+ solid tumors. Moreover, it received Breakthrough Therapy Designation for HER2-positive colorectal cancer (CRC).
UNASSIGNED: We review preclinical and clinical data of T-DXd, focusing on early-phase ongoing trials exploring combination therapies to enhance the activity of T-DXd in HER2-expressing solid tumors.
UNASSIGNED: The clinical use of T-DXd still raises questions about selection of patients, treatment duration, prioritization over other approved ADCs, and management of resistance. Concerns regarding the toxicity of T-DXd remain, particularly with combinations involving potentially toxic drugs. Advancements in biomarker identification and combination therapies offer promising avenues to enhance efficacy and overcome resistance to T-DXd, ultimately improving outcomes for patients with cancer.