Xie Banghong, Chen Chao, Cai Haolin, Wang Lili, Chen Mulan, Liu Jian, Wu Fan, Huang Weiwei
Department of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China.
School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China.
Oncol Ther. 2025 Sep 15. doi: 10.1007/s40487-025-00379-7.
Metastatic triple-negative breast cancer (TNBC) lacks actionable targets, and chemotherapy yields median progression-free survival (mPFS) of 4.6-9.7 months and median overall survival (mOS) of 12.6-26.3 months. Immune checkpoint inhibitors (ICIs) and poly (ADP-ribose) polymerase (PARP) inhibitors only help subsets (objective response rate [ORR] of ~ 5% and ~ 12%, respectively). Antibody-drug conjugates (ADCs) have emerged as a leading therapeutic strategy: sacituzumab govitecan extended mPFS to 5.6 months (ASCENT trial), SKB264 to 6.7 months, and datopotamab deruxtecan achieved an ORR of 79%. In Human epidermal growth factor receptor 2 (HER2)-low TNBC, trastuzumab deruxtecan prolonged OS to 18.2 months, while disitamab vedotin and SHR-A1811 achieved ORRs of 26% and 60%, respectively. ADCs targeting Human epidermal growth factor receptor 3 (HER3)-, Nectin-4-, LIV-1- and folate receptor α (FRα) showed responses in 22%-54% of cases. Resistance can arise via antigen loss, endocytic defects, lysosomal failure, and efflux pumps. Bispecific ADCs, linker optimization, and combination regimens (ICI, PARPi) are under investigation. Future efforts will focus on targeting epidermal growth factor receptor (EGFR) and FRα and on developing multimodal immunovascular strategies to sustain clinical benefit.
转移性三阴性乳腺癌（TNBC）缺乏可操作的靶点，化疗的中位无进展生存期（mPFS）为4.6 - 9.7个月，中位总生存期（mOS）为12.6 - 26.3个月。免疫检查点抑制剂（ICIs）和聚（ADP - 核糖）聚合酶（PARP）抑制剂仅对部分患者有效（客观缓解率[ORR]分别约为5%和12%）。抗体药物偶联物（ADCs）已成为一种主要的治疗策略：戈沙妥珠单抗将mPFS延长至5.6个月（ASCENT试验），SKB264延长至6.7个月，德曲妥珠单抗的ORR达到79%。在人表皮生长因子受体2（HER2）低表达的TNBC中，德曲妥珠单抗将总生存期延长至18.2个月，而迪西他单抗维泊妥珠单抗和SHR - A1811的ORR分别达到26%和60%。靶向人表皮生长因子受体3（HER3）、Nectin - 4、LIV - 1和叶酸受体α（FRα）的ADCs在22% - 54%的病例中显示出疗效。耐药可通过抗原丢失、内吞缺陷、溶酶体功能障碍和外排泵产生。双特异性ADCs、连接子优化和联合治疗方案（ICI、PARPi）正在研究中。未来的努力将集中在靶向表皮生长因子受体（EGFR）和FRα以及开发多模式免疫血管策略以维持临床获益。
