Belani Neel, Donnelly Anjali, Spira Alexander
Virginia Cancer Specialists, Fairfax, VA, USA.
University of Michigan, Ann Arbor, MI, USA.
Expert Opin Biol Ther. 2025 Jul;25(7):695-701. doi: 10.1080/14712598.2025.2519532. Epub 2025 Jun 15.
Despite recent treatment breakthroughs, non-small cell lung cancer (NSCLC) remains the highest cause of cancer-related mortality. New therapies are urgently needed, particularly in patients without actionable genomic alterations (AGAs), who currently receive a combination of chemotherapy and anti-PD1/PD-L1 therapy. Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate combining an antibody against Trop-2 and an exatecan payload which has shown activity in both breast cancer and NSCLC. With several drugs in this class, it is important to understand their activity and limitations in different subtypes of NSCLC.
The literature was reviewed for trials demonstrating activity of their preliminary and/or final results, Dato-DXd, was studied across multiple clinical trials, including the Phase 1 TROPION-PanTumor01 and Phase 3 TROPION-Lung01 studies that are deemed pivotal in demonstrating its efficacy across different patients.
Dato-DXd is a promising new option for NSCLC treatment with clear evidence of activity, shown early signals of efficacy, particularly in non-squamous NSCLC and patients with AGAs. However, patient selection remains paramount for future clinical development. Further research is necessary to optimize dosing strategies, manage adverse events, and better understand its role in both frontline and relapsed/refractory treatment settings as part of combination therapy, as well as neoadjuvant therapy prior to surgery.
尽管近期治疗取得了突破，但非小细胞肺癌（NSCLC）仍是癌症相关死亡的首要原因。迫切需要新的治疗方法，特别是对于没有可操作基因组改变（AGA）的患者，他们目前接受化疗和抗PD1/PD-L1治疗的联合方案。达波他单抗德卢替康（Dato-DXd）是一种抗体药物偶联物，它将抗Trop-2抗体与依喜替康有效载荷相结合，已在乳腺癌和NSCLC中显示出活性。对于这类药物中的几种，了解它们在NSCLC不同亚型中的活性和局限性很重要。
对文献进行了综述，以查找证明其初步和/或最终结果活性的试验，Dato-DXd在多项临床试验中进行了研究，包括1期TROPION-PanTumor01试验和3期TROPION-Lung01试验，这两项试验在证明其对不同患者的疗效方面被视为关键试验。
Dato-DXd是NSCLC治疗的一个有前景的新选择，有明确的活性证据，显示出早期疗效信号，特别是在非鳞状NSCLC和有AGA的患者中。然而，患者选择对于未来的临床开发仍然至关重要。有必要进一步研究以优化给药策略、管理不良事件，并更好地了解其在联合治疗中的一线和复发/难治性治疗环境以及手术前新辅助治疗中的作用。
