维迪西妥单抗单药或联合免疫治疗对局部晚期或转移性尿路上皮癌的有效性和安全性：一项系统评价和Meta分析

Efficacy and Safety of Disitamab Vedotin Alone or in Combination with Immunotherapy for Locally Advanced or Metastatic Urothelial Carcinoma: A Systematic Review and Meta-Analysis

摘要: 背景：维迪西妥单抗是一种新型的抗HER2抗体–药物偶联物，在局部晚期或转移性尿路上皮癌中显示出了初步疗效。本研究旨在系统评价维迪西妥单药或联合免疫治疗的有效性和安全性。方法：系统检索PubMed、Web of Science、Cochrane Library、Embase数据库。纳入前瞻性研究，包括RCT和单臂II期试验。采用随机效应模型进行Meta分析。结果：共纳入6个研究，包括436例患者。其中5项为单臂研究，1项为随机对照试验(RCT)。总的客观缓解率(ORR)为62% (95% CI: 49%~74%)，疾病控制率(DCR)为89% (95% CI: 84%~93%)，中位无进展生存期(PFS)为7.9个月(95% CI: 5.0~12.4)。43% (95% CI: 30%~58%)患者发生≥3级的治疗相关不良事件，最常见的为中性粒细胞减少(8%)、γ-谷氨酰转移酶升高(7%)和周围神经病变(6%)。然而，上述结果主要基于单臂研究，研究间存在显著异质性(I² > 50%)，联合治疗优势的观察仅为探索性亚组分析，证据强度有限。结论：维迪西妥单抗单药或联合免疫治疗在局部晚期或转移性尿路上皮癌患者中显示出有前景的抗肿瘤活性和可控的安全性。初步观察提示联合治疗可能具有更强的疗效，但这一发现需在设计良好的头对头随机对照试验中进一步验证。当前证据主要来自小样本单臂研究，结论应被视为探索性的。

Abstract: Background: Disitamab vedotin is a novel anti-HER2 antibody-drug conjugate that has shown preliminary efficacy in locally advanced or metastatic urothelial carcinoma (la/mUC). This study aimed to systematically evaluate the efficacy and safety of disitamab vedotin monotherapy or in combination with immunotherapy. Methods: A systematic search was conducted in PubMed, Web of Science, Cochrane Library, and Embase databases. Prospective studies, including RCTs and single-arm phase II trials, were included. Meta-analyses were performed using random-effects models. Results: Six studies comprising 436 patients were included. Five were single-arm studies and one was a randomized controlled trial (RCT). The pooled objective response rate (ORR) was 62% (95% CI: 49%~74%), disease control rate (DCR) was 89% (95% CI: 84%~93%), and median progression-free survival was 7.9 months (95% CI: 5.0~12.4). Grade ≥ 3 treatment-related adverse events occurred in 43% (95% CI: 30%~58%), with the most common being neutropenia (8%), γ-glutamyltransferase elevation (7%), and peripheral neuropathy (6%). However, these findings are primarily derived from single-arm studies with substantial heterogeneity (I² > 50%), and the observed benefit of combination therapy is hypothesis-generating based on exploratory subgroup analyses. Conclusions: Disitamab vedotin monotherapy or in combination with immunotherapy demonstrates promising antitumor activity with a manageable safety profile in patients with la/mUC. Preliminary observations suggest that combination therapy may offer enhanced efficacy; however, this finding warrants confirmation in well-designed head-to-head randomized controlled trials. The current evidence, largely derived from small-sample single-arm studies, should be interpreted as exploratory.