本探索性分析评估了来自EV-301研究的中位随访时间约2年的安福替单抗与化疗的疗效和安全性数据。入组病例为局部晚期/转移性尿路上皮癌患者，之前接受铂类化疗并在程序性细胞死亡蛋白1/配体1抑制剂治疗期间或治疗后出现疾病进展，随机分配至安福替单抗组或化疗组（多西他赛、紫杉醇、芬氟尼）。终点包括总生存期（主要终点）、无进展生存期（PFS）、客观反应和安全性。共纳入608例患者（安福替单抗组n=301；化疗组n=307）。在中位随访时间为23.75个月时，发生了444例死亡事件（安福替单抗组n=207；化疗组n=237）。安福替单抗组与化疗组相比，死亡风险降低30%（HR 0.70 [95% CI, 0.58 to 0.85]；单侧，log-rank P = 0.00015）；安福替单抗组的PFS得到改善（HR 0.63 [95% CI, 0.53 to 0.76]；单侧，log-rank P < 0.00001）。与化疗相比，安福替单抗的治疗相关不良事件发生率为93.9%，化疗的为91.8%；≥3级不良事件发生率分别为52.4%和50.5%。化疗组相对于安福替单抗组更常见的≥3级治疗相关性粒细胞减少（14.1% vs 6.1%）、白细胞减少（7.2% vs 1.4%）和贫血（7.9% vs 2.7%）；安福替单抗组相对于化疗组更常见的麻疹样皮疹（7.4% vs 0%）、疲劳（6.8% vs 4.5%）和外周感觉神经病变（5.1% vs 2.1%）。在特殊意义的不良事件中，接受安福替单抗的患者中有47.3%出现治疗相关性皮肤反应，接受化疗的患者中为15.8%；外周神经病变分别为48.0%和31.6%，高血糖分别为6.8%和0.3%。在中位随访时间为约2年后，安福替单抗相对于化疗仍保持具有临床意义的总生存期益处，与EV-301主要分析结果一致；无进展生存期和总体响应益处保持一致。不良事件可管理，未观察到新的安全信号。 © 2023 Elsevier Ltd. 出版。

This exploratory analysis evaluated efficacy and safety data for enfortumab vedotin versus chemotherapy over median follow-up of approximately 2 years from EV-301.Patients with locally advanced/metastatic urothelial carcinoma with prior platinum-containing chemotherapy and disease progression during/after programmed cell death protein 1/ligand 1 inhibitor treatment were randomized to enfortumab vedotin or chemotherapy (docetaxel, paclitaxel, vinflunine). Endpoints were overall survival (primary), progression-free survival (PFS), objective response, and safety.In total, 608 patients were included (enfortumab vedotin, n = 301; chemotherapy, n = 307). With median follow-up of 23.75 months, 444 deaths had occurred (enfortumab vedotin, n = 207; chemotherapy, n = 237). Risk of death was reduced by 30% with enfortumab vedotin versus chemotherapy (HR 0.70 [95% CI, 0.58 to 0.85]; 1-sided, log-rank P = 0.00015); PFS improved with enfortumab vedotin (HR 0.63 [95% CI, 0.53 to 0.76]; 1-sided, log-rank P < 0.00001). Treatment-related adverse event rates were 93.9% for enfortumab vedotin and 91.8% for chemotherapy; grade ≥ 3 event rates were 52.4% and 50.5%, respectively. Grade ≥ 3 treatment-related decreased neutrophil count (14.1% vs 6.1%), decreased white blood cell count (7.2% vs 1.4%), and anemia (7.9% vs 2.7%) were more common with chemotherapy versus enfortumab vedotin; maculopapular rash (7.4% vs 0%), fatigue (6.8% vs 4.5%), and peripheral sensory neuropathy (5.1% vs 2.1%) were more common with enfortumab vedotin. Of special interest adverse events, treatment-related skin reactions occurred in 47.3% of patients receiving enfortumab vedotin and 15.8% of patients receiving chemotherapy; peripheral neuropathy occurred in 48.0% versus 31.6%, respectively, and hyperglycemia in 6.8% versus 0.3%.After median follow-up of approximately 2 years, enfortumab vedotin maintained clinically meaningful overall survival benefit versus chemotherapy, consistent with findings from the EV-301 primary analysis; PFS and overall response benefit remained consistent. Adverse events were manageable; no new safety signals were observed.Copyright © 2023. Published by Elsevier Ltd.