Gogtay Maya, Aimalla Nikhila, Thirugnanasambandam Ram Prakash, Ganti Apar Kishor
Division of Oncology-Hematology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-6840, USA.
Department of Internal Medicine - Pediatrics, Marshfield Clinic Health System, Marshfield, WI, 54449, USA.
Onco Targets Ther. 2025 Apr 23;18:575-584. doi: 10.2147/OTT.S466220. eCollection 2025.
Lung cancer is the leading cause of global cancer mortality, accounting for an estimated 2 million diagnoses and 1.8 million deaths annually. Treatment choices for non-small cell lung cancer include surgery, radiation therapy, chemotherapy, immunotherapy, or molecularly targeted therapy. Antibody-drug conjugates (ADCs), often likened to "biological missiles", are rapidly evolving as a targeted therapeutic approach. Trophoblast cell surface antigen 2 (Trop 2) is a 36-kDa cell surface glycoprotein, which is expressed in various cancers. This fuels oncogenic signaling pathways, driving tumor advancement, invasion, and spread. Its limited expression in healthy human tissues underscores its potential as a target for cancer treatment. Datopotamab Deruxtecan (Dato-Dxd) is an investigational ADC that targets Trop-2. This review discusses the current treatment landscape involving therapy with Dato-Dxd for advanced NSCLC. Dato-DXd was first used in metastatic solid tumors in the Phase I TROPION-PanTumor 01 trial, which showed promising antitumor activity in the previously pretreated NSCLC cohort and a manageable safety outline. In TROPION-Lung01, Dato-DXD was studied in metastatic NSCLC patients who were previously treated and showed an objective response rate of 26.4% (Dato-DXd). Other trials, including TROPION PanTumor 02, ICARUS - Lung 01, and TROPION Lung 05, showed comparable results. Dato-DXd used along with pembrolizumab, with or without systemic chemotherapy, in TROPION Lung 02 with promising efficacy results. The most common any-grade treatment-emergent adverse events were stomatitis, nausea, and hair loss, mostly grade 1-2. There are several clinical trials in the pipeline using Dato-DXd in the front-line metastatic setting and resectable NSCLC patients. Dato-DXd is currently pending approval from the US Food and Drug Administration (FDA). If approved, datopotamab deruxtecan will be the first TROP2-directed antibody-drug conjugate for non-small cell lung cancer.
肺癌是全球癌症死亡的主要原因，估计每年有200万例诊断病例和180万例死亡病例。非小细胞肺癌的治疗选择包括手术、放射治疗、化疗、免疫治疗或分子靶向治疗。抗体药物偶联物（ADC）常被比作“生物导弹”，作为一种靶向治疗方法正在迅速发展。滋养层细胞表面抗原2（Trop 2）是一种36 kDa的细胞表面糖蛋白，在多种癌症中均有表达。这加剧了致癌信号通路，推动肿瘤进展、侵袭和扩散。其在健康人体组织中的有限表达突出了其作为癌症治疗靶点的潜力。达托泊单抗德鲁替康（Dato-Dxd）是一种靶向Trop-2的研究性ADC。本综述讨论了目前使用Dato-Dxd治疗晚期非小细胞肺癌的治疗情况。Dato-DXd首次用于I期TROPION-PanTumor 01试验中的转移性实体瘤，该试验在先前接受过治疗的非小细胞肺癌队列中显示出有前景的抗肿瘤活性和可控的安全性概况。在TROPION-Lung01中，对先前接受过治疗的转移性非小细胞肺癌患者进行了Dato-DXD研究，客观缓解率为26.4%（Dato-DXd）。其他试验，包括TROPION PanTumor 02、ICARUS-Lung 01和TROPION Lung 05，也显示了类似的结果。在TROPION Lung 02中，Dato-DXd与帕博利珠单抗联合使用，无论是否进行全身化疗，均产生了有前景的疗效结果。最常见的任何级别的治疗中出现的不良事件为口腔炎、恶心和脱发，大多为1-2级。目前有多项临床试验正在进行中，将Dato-DXd用于一线转移性和可切除非小细胞肺癌患者。Dato-DXd目前正在等待美国食品药品监督管理局（FDA）的批准。如果获得批准，达托泊单抗德鲁替康将成为首个用于非小细胞肺癌的TROP2导向抗体药物偶联物。
