Xieqiao Yan, Juan Li, Huayan Xu, Yiqiang Liu, Li Zhou, Siming Li, Xiaowen Wu, Bixia Tang, Zhihong Chi, Chuanliang Cui, Lu Si, Lili Mao, Bin Lian, Xuan Wang, Rong Duan, Caili Li, Jianmin Fang, Jun Guo, Xinan Sheng
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引用次数: 0
Abstract
Background: Human epidermal growth factor receptor 2 (HER2) has emerged as a new target for metastatic urothelial carcinomas (mUCs). Disitamab vedotin (DV), an anti-HER2 antibody-drug conjugate (ADC), demonstrates a promising efficacy in patients with HER2-positive mUC. However, the role of DV in HER2-negative and HER2-low mUCs remains unknown.
Methods: Patients with HER2-negative and HER2-low (immunohistochemistry [IHC] 0 or 1+) mUCs who received ≥1 line of systemic chemotherapy were included. Patients received 2 mg/kg DV intravenously once every 2 weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.
Findings: Nineteen patients with UC were enrolled from September 2019 to December 2021. The median age was 64.0 years. 15 patients (79%) had visceral metastases. HER2 IHC 0 and 1+ were detected in 6 and 13 patients, respectively. As of September 30, 2022, the confirmed ORR was 31.6% (95% confidence interval [CI]: 12.6, 56.6), and the disease control rate was 94.7% (18/19). The median PFS and OS were 5.5 (95% CI: 3.9, 5.7) and 16.4 (6.8, 26.8) months, respectively. Common treatment related adverse events were mostly grade 1 or 2, including leukopenia (52.6%) and hypoesthesia (47.4%).
Conclusions: This is the first exploratory trial demonstrating substantial anti-tumor activity and a manageable safety profile using a HER2-targeting agent in patients with HER2-low mUC. This study was registered at ClinicalTrials.gov (ClinicalTrials.gov: NCT04073602).
Funding: The study was funded by the Natural Science Foundation of China, the Natural Science Foundation of Tibet Autonomous Region, the Beijing Xisike Clinical Oncology Research Foundation, and RemeGen, Ltd.
期刊介绍：
Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically.
Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.
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