Nakamura Kazutaka, Kobari Yuki, Ishiyama Yudai, Kondo Hanae, Inakawa Toru, Nemoto Yuki, Fukuda Hironori, Yoshida Kazuhiko, Iizuka Junpei, Shimmura Hiroaki, Kobayashi Hiroshi, Hashimoto Yasunobu, Ishida Hideki, Kondo Tsunenori, Takagi Toshio
Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
Department of Urology, Tokyo Women's Medical University, Tokyo, Japan;
In Vivo. 2025 Sep-Oct;39(5):2766-2776. doi: 10.21873/invivo.14075.
BACKGROUND/AIM: The EV-301 trial demonstrated the efficacy of enfortumab vedotin (EV) as a third-line treatment for metastatic urothelial carcinoma (mUC), showing significant improvement in overall survival (OS) and progression-free survival (PFS) compared to chemotherapy in patients previously treated with platinum-based therapy and immune checkpoint inhibitors. In real-world clinical practice, patients undergoing third-line treatment often have poor baseline health status, leading to the off-label use of EV in populations ineligible for clinical trials. This study aimed to evaluate the treatment outcomes of EV in both EV-301 trial-eligible and -ineligible patients.
Fifty-eight patients with mUC treated with EV across five Institutions were retrospectively evaluated and stratified based on the EV-301 trial eligibility criteria. Patients with an Eastern Cooperative Oncology Group performance status of ≥2, baseline hemoglobin level of <9 g/dl, creatinine clearance <30 ml/min, or other protocol-defined criteria were analyzed. Treatment outcomes were assessed for both groups.
Of the 58 patients, 33 (56.9%) met the EV-301 trial eligibility criteria. No significant differences were observed in PFS (median: 9.2 7.1 months, for eligible ineligible patients) and OS (15.4 8.9 months). Although the objective response rate was higher in the eligible group (54.6% 28.0%), there was no significant difference in the disease control rate (78.8% 80.0%). Adverse events (AEs) of any grade were more frequent in the eligible group (93.9% 64.0%), but the incidence of grade ≥3 AEs did not differ significantly (12.1% 8.0%).
The findings of this multi-institutional study highlight the feasibility of EV treatment in EV-301 trial-ineligible patients with mUC, supporting its potential applicability in both trial-eligible and -ineligible groups.
背景/目的：EV-301试验证明了恩杂鲁胺（EV）作为转移性尿路上皮癌（mUC）三线治疗的疗效，与接受铂类疗法和免疫检查点抑制剂治疗的患者相比，其总生存期（OS）和无进展生存期（PFS）有显著改善。在现实世界的临床实践中，接受三线治疗的患者基线健康状况往往较差，导致EV在不符合临床试验条件的人群中被超适应症使用。本研究旨在评估EV在符合和不符合EV-301试验条件的患者中的治疗效果。
回顾性评估了五个机构接受EV治疗的58例mUC患者，并根据EV-301试验的入选标准进行分层。分析了东部肿瘤协作组体能状态≥2、基线血红蛋白水平<9 g/dl、肌酐清除率<30 ml/min或其他方案定义标准的患者。评估了两组的治疗效果。
58例患者中，33例（56.9%）符合EV-301试验入选标准。符合标准与不符合标准的患者在PFS（中位数：符合标准者为9.2个月，不符合标准者为7.1个月）和OS（分别为15.4个月和8.9个月）方面未观察到显著差异。虽然符合标准组的客观缓解率较高（54.6%对28.0%），但疾病控制率无显著差异（78.8%对80.0%）。符合标准组任何级别的不良事件（AE）更常见（93.9%对64.0%），但≥3级AE的发生率无显著差异（12.1%对8.0%）。
这项多机构研究的结果突出了EV治疗不符合EV-301试验条件的mUC患者的可行性，支持其在符合和不符合试验条件的两组中的潜在适用性。
