Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma.
Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma.
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DOI：
10.1056/nejmoa2035807
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发表时间：
2021-03-25
期刊：
影响因子：
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通讯作者：
Petrylak DP
中科院分区：
文献类型：
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作者：
Powles T;Rosenberg JE;Sonpavde GP;Loriot Y;Durán I;Lee JL;Matsubara N;Vulsteke C;Castellano D;Wu C;Campbell M;Matsangou M;Petrylak DP
晚期尿路上皮癌患者接受含铂化疗和程序性细胞死亡蛋白-1/程序性死亡配体1（PD-1/L1）抑制剂治疗后的总生存率较差。EV-301是一项在既往接受过含铂化疗并在PD-1/L1抑制剂治疗期间或之后发生疾病进展的局部晚期或转移性尿路上皮癌患者中进行的恩福妥尤单抗vedotin全球、开放标签、III期试验。患者以1：1的比例随机接受enfortumab vedotin 1.25 mg/kg，在28天周期的第1、8和15天给药，或接受药物选择的标准多西他赛、紫杉醇或长春氟宁给药。主要终点是总生存期。总体而言，608例患者随机接受恩福妥单抗（n=301）或化疗（n=307）。截至2020年7月15日，共发生301例死亡（恩福妥单抗vedotin，n=134;化疗，n=167）。在预先规定的中期分析中，中位随访时间为11.1个月。与化疗相比，恩福妥单抗vedotin延长了总生存期（HR=0.70 [95% CI：0.56-0.89]; P=0.00142;中位总生存期：分别为12.88 vs 8.97个月）。恩福妥尤单抗组的无进展生存期也长于化疗组（HR=0.62 [95% CI：0.51-0.75]; P<0.00001;中位无进展生存期：分别为5.55 vs 3.71个月）。恩福妥尤单抗组（93.9%）和化疗组（91.8%）的治疗相关不良事件发生率相当;严重程度≥3级的事件也相当（分别为51.4%和49.8%）。与标准化疗相比，Enfortumab vedotin显著延长了既往接受过铂类药物治疗和PD-1/L1抑制剂的局部晚期或转移性尿路上皮癌患者的生存期。（ClinicalTrials.gov编号，NCT 03474107）
Patients with advanced urothelial carcinoma have poor overall survival after platinum-containing chemotherapy and programmed cell death protein-1/programmed death-ligand 1 (PD-1/L1) inhibitor treatment. EV-301 is a global, open-label, phase 3 trial of enfortumab vedotin in patients with locally advanced or metastatic urothelial carcinoma who had previously received a platinum-containing chemotherapy and experienced disease progression during or following treatment with a PD-1/L1 inhibitor. Patients were randomized 1:1 to receive enfortumab vedotin 1.25 mg/kg on Days 1, 8, and 15 of a 28-day cycle, or investigator-chosen standard docetaxel, paclitaxel, or vinflunine. The primary endpoint was overall survival. Overall, 608 patients were randomized to enfortumab vedotin (n=301) or chemotherapy (n=307). As of July 15, 2020, a total of 301 deaths (enfortumab vedotin, n=134; chemotherapy, n=167) had occurred. At the prespecified interim analysis, the median follow-up was 11.1 months. Overall survival was prolonged with enfortumab vedotin compared with chemotherapy (HR=0.70 [95% CI: 0.56–0.89]; P=0.00142; median overall survival: 12.88 vs 8.97 months, respectively). Progression-free survival was also longer in the enfortumab vedotin group compared with the chemotherapy group (HR=0.62 [95% CI: 0.51–0.75]; P<0.00001; median progression-free survival: 5.55 vs 3.71 months, respectively). Rates of treatment-related adverse events were comparable between enfortumab vedotin (93.9%) and chemotherapy (91.8%) groups; events of grade ≥3 severity were also comparable (51.4% and 49.8%, respectively). Enfortumab vedotin significantly prolonged survival over standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma who previously received platinum-based treatment and a PD-1/L1 inhibitor. (ClinicalTrials.gov number, NCT03474107)