Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma.
Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma.
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DOI：
10.1056/nejmoa2034442
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发表时间：
2021-06-03
期刊：
影响因子：
--
通讯作者：
Galsky MD
中科院分区：
文献类型：
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作者：
Bajorin DF;Witjes JA;Gschwend JE;Schenker M;Valderrama BP;Tomita Y;Bamias A;Lebret T;Shariat SF;Park SH;Ye D;Agerbaek M;Enting D;McDermott R;Gajate P;Peer A;Milowsky MI;Nosov A;Neif Antonio J Jr;Tupikowski K;Toms L;Fischer BS;Qureshi A;Collette S;Unsal-Kacmaz K;Broughton E;Zardavas D;Koon HB;Galsky MD
高危肌浸润性尿路上皮癌根治性手术后辅助治疗的作用尚不清楚。在一项3期、多中心、双盲、随机对照试验中，我们将接受根治性手术的肌肉侵袭性尿路上皮癌患者按1:1的比例接受nivolumab （240 mg静脉注射）或安慰剂治疗，每2周一次，持续1年。允许在试验开始前以顺铂为基础的新辅助化疗。主要终点是所有患者（意向治疗人群）和肿瘤程序性死亡配体1 （PD-L1）表达水平为1%或更高的患者的无病生存期。在尿路外无复发的生存期是次要终点。共有353名患者接受纳武单抗治疗，356名患者接受安慰剂治疗。在意向治疗人群中，纳武单抗组的中位无病生存期为20.8个月（95%置信区间[CI]， 16.5至27.6），安慰剂组的中位无病生存期为10.8个月（95% CI， 8.3至13.9）。纳武单抗组在6个月时存活且无疾病的患者比例为74.9%，安慰剂组为60.3%（疾病复发或死亡的风险比为0.70;98.22% CI, 0.55 ~ 0.90； P<0.001）。PD-L1表达水平≥1%的患者比例分别为74.5%和55.7%（风险比0.55;98.72% CI, 0.35 ~ 0.85； P<0.001）。在意向治疗人群中，纳武单抗组尿路外无复发的中位生存期为22.9个月（95% CI， 19.2至33.4），安慰剂组为13.7个月（95% CI， 8.4至20.3）。纳武单抗组在6个月时存活且无尿路外复发的患者比例为77.0%，安慰剂组为62.7%（尿路外复发或死亡的风险比为0.72；95% CI为0.59至0.89）。PD-L1表达水平≥1%的患者比例分别为75.3%和56.7%（风险比0.55;95% CI 0.39 ~ 0.79）。治疗相关的3级或以上不良事件发生在纳武单抗组的17.9%和安慰剂组的7.2%。在纳武单抗组中有2例治疗相关肺炎死亡。在这项涉及接受根治性手术的高风险肌肉侵袭性尿路上皮癌患者的试验中，在有意治疗人群和PD-L1表达水平为1%或更高的患者中，辅助nivolumab的无病生存期比安慰剂更长。（由Bristol Myers Squibb和Ono Pharmaceutical资助；CheckMate 274 ClinicalTrials.gov号码，NCT02632409。）
The role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery is not clear. In a phase 3, multicenter, double-blind, randomized, controlled trial, we assigned patients with muscle-invasive urothelial carcinoma who had undergone radical surgery to receive, in a 1:1 ratio, either nivolumab (240 mg intravenously) or placebo every 2 weeks for up to 1 year. Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. The primary end points were disease-free survival among all the patients (intention-to-treat population) and among patients with a tumor programmed death ligand 1 (PD-L1) expression level of 1% or more. Survival free from recurrence outside the urothelial tract was a secondary end point. A total of 353 patients were assigned to receive nivolumab and 356 to receive placebo. The median disease-free survival in the intention-to-treat population was 20.8 months (95% confidence interval [CI], 16.5 to 27.6) with nivolumab and 10.8 months (95% CI, 8.3 to 13.9) with placebo. The percentage of patients who were alive and disease-free at 6 months was 74.9% with nivolumab and 60.3% with placebo (hazard ratio for disease recurrence or death, 0.70; 98.22% CI, 0.55 to 0.90; P<0.001). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 74.5% and 55.7%, respectively (hazard ratio, 0.55; 98.72% CI, 0.35 to 0.85; P<0.001). The median survival free from recurrence outside the urothelial tract in the intention-to-treat population was 22.9 months (95% CI, 19.2 to 33.4) with nivolumab and 13.7 months (95% CI, 8.4 to 20.3) with placebo. The percentage of patients who were alive and free from recurrence outside the urothelial tract at 6 months was 77.0% with nivolumab and 62.7% with placebo (hazard ratio for recurrence outside the urothelial tract or death, 0.72; 95% CI, 0.59 to 0.89). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 75.3% and 56.7%, respectively (hazard ratio, 0.55; 95% CI, 0.39 to 0.79). Treatment-related adverse events of grade 3 or higher occurred in 17.9% of the nivolumab group and 7.2% of the placebo group. Two treatment-related deaths due to pneumonitis were noted in the nivolumab group. In this trial involving patients with high-risk muscle-invasive urothelial carcinoma who had undergone radical surgery, disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression level of 1% or more. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 274 ClinicalTrials.gov number, NCT02632409.)
影响因子：
2
作者：
Pradère B;Thibault C;Vetterlein MW;Leow JJ;Peyronnet B;Rouprêt M;Seisen T
通讯作者：
Seisen T