Lisberg Aaron, Huppert Laura A, Halmos Balazs, Ledezma Blanca, Soto-Romano Vanessa, Traina Tiffany A
David Geffen School of Medicine at UCLA, Santa Monica, CA, USA.
UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
Oncologist. 2025 Jul 23. doi: 10.1093/oncolo/oyaf225.
Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate comprised of a topoisomerase I inhibitor payload and a monoclonal antibody directed to trophoblast cell-surface antigen 2, a protein that is broadly expressed in several types of solid tumors. In the TROPION-Lung01 phase III trial (NCT04656652), Dato-DXd demonstrated statistically significant improvement in median progression-free survival (mPFS) over docetaxel (4.4 vs. 3.7 months, hazard ratio [HR]=0.75, 95% confidence interval [CI], 0.62-0.91, P=.004]) in patients with previously treated metastatic non-small cell lung cancer (mNSCLC). Improvement in PFS was demonstrated in patients with nonsquamous mNSCLC (mPFS: 5.5 vs. 3.6 months, HR = 0.63, 95% CI, 0.51-0.79) and those with NSQ mNSCLC and actionable genomic alterations (mPFS: 5.7 vs 2.6 months, HR = 0.35, 95% CI, 0.21-0.60). A pooled analysis of previously treated patients with epidermal growth factor receptor mutation-positive NSCLC from TROPION-Lung01 and TROPION-Lung05 (NCT04484142) treated with Dato-DXd supported clinical activity (mPFS: 5.8 months, 95% CI, 5.4-8.2). In the TROPION-Breast01 phase III trial (NCT05104866), Dato-DXd demonstrated statistically significant improvement in mPFS over the investigator's choice of chemotherapy (6.9 vs. 4.9 months, HR = 0.63, 95% CI, 0.52-0.76, P<.0001) in patients with previously treated post-endocrine therapy hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. Dato-DXd also demonstrated a distinct safety profile in both trials. The successful implementation of any new anticancer therapy requires learning how to prevent, monitor, and manage treatment-related adverse events (AE). Information can be gained from real-world clinical practices, institutional approaches, and multidisciplinary teams who treat patients with Dato-DXd to provide a better patient experience and improved outcomes. Here, we discuss practical insights and management and treatment of key AEs from Dato-DXd, including oral mucositis/stomatitis, nausea and vomiting, ocular surface events, and interstitial lung disease garnered from a multidisciplinary team of health care professionals experienced in treating patients with Dato-DXd.
德曲妥珠单抗（Datopotamab deruxtecan，Dato-DXd）是一种抗体药物偶联物，由一种拓扑异构酶I抑制剂有效载荷和一种靶向滋养层细胞表面抗原2的单克隆抗体组成，该蛋白在多种实体瘤中广泛表达。在TROPION-Lung01 III期试验（NCT04656652）中，与多西他赛相比，Dato-DXd在既往接受过治疗的转移性非小细胞肺癌（mNSCLC）患者的中位无进展生存期（mPFS）方面显示出统计学上的显著改善（4.4个月对3.7个月，风险比[HR]=0.75，95%置信区间[CI]，0.62-0.91，P=0.004）。非鳞状mNSCLC患者（mPFS：5.5个月对3.6个月，HR = 0.63，95% CI，0.51-0.79）以及非鳞状mNSCLC且有可操作基因组改变的患者（mPFS：5.7个月对2.6个月，HR = 0.35，95% CI，0.21-0.60）的PFS均有改善。对TROPION-Lung01和TROPION-Lung05（NCT04484142）中既往接受过治疗的表皮生长因子受体突变阳性NSCLC患者使用Dato-DXd进行的汇总分析支持了其临床活性（mPFS：5.8个月，95% CI，5.4-8.2）。在TROPION-Breast01 III期试验（NCT05104866）中，与研究者选择的化疗相比，Dato-DXd在既往接受过内分泌治疗的激素受体阳性/人表皮生长因子受体2阴性转移性乳腺癌患者的mPFS方面显示出统计学上的显著改善（6.9个月对4.9个月，HR = 0.63，95% CI，0.52-0.76，P<0.0001）。Dato-DXd在两项试验中也显示出独特的安全性特征。任何新的抗癌治疗的成功实施都需要了解如何预防、监测和管理与治疗相关的不良事件（AE）。可以从真实世界的临床实践、机构方法以及治疗使用Dato-DXd患者的多学科团队中获取信息，以提供更好的患者体验并改善治疗结果。在此，我们讨论来自Dato-DXd的关键AE的实际见解以及管理和治疗方法，包括口腔黏膜炎/口腔炎、恶心和呕吐、眼表事件以及间质性肺病，这些是从治疗使用Dato-DXd患者的多学科医疗专业团队中获得的经验。
