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Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial.
The Lancet ( IF 98.4 ) Pub Date : 2020-05-16 , DOI: 10.1016/s0140-6736(20)30230-0
Matthew D Galsky , José Ángel Arranz Arija , Aristotelis Bamias , Ian D Davis , Maria De Santis , Eiji Kikuchi , Xavier Garcia-del-Muro , Ugo De Giorgi , Marina Mencinger , Kouji Izumi , Stefano Panni , Mahmut Gumus , Mustafa Özgüroğlu , Arash Rezazadeh Kalebasty , Se Hoon Park , Boris Alekseev , Fabio A Schutz , Jian-Ri Li , Dingwei Ye , Nicholas J Vogelzang , Sandrine Bernhard , Darren Tayama , Sanjeev Mariathasan , Almut Mecke , AnnChristine Thåström , Enrique Grande

BACKGROUND Atezolizumab can induce sustained responses in metastatic urothelial carcinoma. We report the results of IMvigor130, a phase 3 trial that compared atezolizumab with or without platinum-based chemotherapy versus placebo plus platinum-based chemotherapy in first-line metastatic urothelial carcinoma. METHODS In this multicentre, phase 3, randomised trial, untreated patients aged 18 years or older with locally advanced or metastatic urothelial carcinoma, from 221 sites in 35 countries, were randomly assigned to receive atezolizumab plus platinum-based chemotherapy (group A), atezolizumab monotherapy (group B), or placebo plus platinum-based chemotherapy (group C). Patients received 21-day cycles of gemcitabine (1000 mg/m2 body surface area, administered intravenously on days 1 and 8 of each cycle), plus either carboplatin (area under the curve of 4·5 mg/mL per min administered intravenously) or cisplatin (70 mg/m2 body surface area administered intravenously) on day 1 of each cycle with either atezolizumab (1200 mg administered intravenously on day 1 of each cycle) or placebo. Group B patients received 1200 mg atezolizumab, administered intravenously on day 1 of each 21-day cycle. The co-primary efficacy endpoints for the intention-to-treat population were investigator-assessed Response Evaluation Criteria in Solid Tumours 1.1 progression-free survival and overall survival (group A vs group C) and overall survival (group B vs group C), which was to be formally tested only if overall survival was positive for group A versus group C. The trial is registered with ClinicalTrials.gov, NCT02807636. FINDINGS Between July 15, 2016, and July 20, 2018, we enrolled 1213 patients. 451 (37%) were randomly assigned to group A, 362 (30%) to group B, and 400 (33%) to group C. Median follow-up for survival was 11·8 months (IQR 6·1-17·2) for all patients. At the time of final progression-free survival analysis and interim overall survival analysis (May 31, 2019), median progression-free survival in the intention-to-treat population was 8·2 months (95% CI 6·5-8·3) in group A and 6·3 months (6·2-7·0) in group C (stratified hazard ratio [HR] 0·82, 95% CI 0·70-0·96; one-sided p=0·007). Median overall survival was 16·0 months (13·9-18·9) in group A and 13·4 months (12·0-15·2) in group C (0·83, 0·69-1·00; one-sided p=0·027). Median overall survival was 15·7 months (13·1-17·8) for group B and 13·1 months (11·7-15·1) for group C (1·02, 0·83-1·24). Adverse events that led to withdrawal of any agent occurred in 156 (34%) patients in group A, 22 (6%) patients in group B, and 132 (34%) patients in group C. 50 (11%) patients in group A, 21 (6%) patients in group B, and 27 (7%) patients in group C had adverse events that led to discontinuation of atezolizumab or placebo. INTERPRETATION Addition of atezolizumab to platinum-based chemotherapy as first-line treatment prolonged progression-free survival in patients with metastatic urothelial carcinoma. The safety profile of the combination was consistent with that observed with the individual agents. These results support the use of atezolizumab plus platinum-based chemotherapy as a potential first-line treatment option for metastatic urothelial carcinoma. FUNDING F Hoffmann-La Roche and Genentech.

中文翻译:

Atezolizumab在转移性尿路上皮癌中接受或不接受化疗(IMvigor130):一项多中心,随机,安慰剂对照的3期临床试验。

背景技术阿托珠单抗可以在转移性尿路上皮癌中诱导持续反应。我们报告了IMvigor130的一项3期试验结果,该试验比较了在一线转移性尿路上皮癌中使用或不使用铂类化疗与安慰剂加铂类化疗的atezolizumab的比较。方法在这项多中心,3期,随机试验中,来自35个国家/地区的221个地点的18岁或18岁以上局部晚期或转移性尿路上皮癌未经治疗的患者被随机分配接受Atezolizumab联合铂类化疗(A组)Atezolizumab单一疗法(B组),或安慰剂加铂类化疗(C组)。患者接受吉西他滨21天周期(1000 mg / m2体表面积,在每个周期的第1天和第8天静脉注射),在每个周期的第1天加用卡铂(曲线下面积为每分钟4·5 mg / mL的静脉内给药面积)或顺铂(70 mg / m2体表面积静脉内给药),同时使用atezolizumab(在第1天静脉给药1200 mg每个周期)或安慰剂。B组患者在每个21天周期的第1天接受1200 mg atezolizumab静脉内给药。意向性治疗人群的共同主要疗效终点是研究者评估的实体瘤反应评估标准1.1无进展生存期和总生存期(A组与C组)和总生存期(B组与C组),仅当A组与C组的总体生存期均为阳性时才进行正式测试。该试验已在ClinicalTrials.gov注册,NCT02807636。发现在2016年7月15日至7月20日之间,2018年,我们招募了1213名患者。A组随机分配了451(37%),B组随机分配了362(30%),C组随机分配了400(33%)。生存的中位随访时间为11·8个月(IQR 6·1-17· 2)适用于所有患者。在进行最终无进展生存期分析和中期总体生存期分析时(2019年5月31日),意向治疗人群的中位无进展生存期为8·2个月(95%CI 6·5-8· 3)在A组中和6·3个月(6·2-7·0)在C组中(分层危险比[HR] 0·82,95%CI 0·70-0·96;单侧p = 0 ·007)。A组中位总生存期中位数为16·0个月(13·9-18·9),C组中位总生存期为13·4个月(12·0-15·2)(0·83、0·69-1·00;一侧p = 0·027)。B组中位生存期中位数为15·7个月(13·1-17·8),C组中位生存期为13·1个月(11·7-15·1)(1·02,0·83-1·24) 。导致停用任何药物的不良事件发生在A组中的156(34%)患者,B组中的22(6%)患者和C组中的132(34%)患者中。50(11%)组患者A,B组中的21名患者(6%)和C组中的27名患者(7%)有不良事件,这些不良事件导致停用了atezolizumab或安慰剂。解释作为铂金的一线治疗,将阿特珠单抗作为一线治疗可延长转移性尿路上皮癌患者的无进展生存期。组合的安全性与单个药剂观察到的一致。这些结果支持使用atezolizumab联合铂类化疗作为转移性尿路上皮癌的潜在一线治疗选择。资金筹集Hoffmann-La Roche和Genentech。B组22例(6%),C组132例(34%)。A组50例(11%),B组21例(6%),B组27例(7%) C有不良事件,导致终止atezolizumab或安慰剂。解释作为铂金的一线治疗,将阿特珠单抗作为一线治疗可延长转移性尿路上皮癌患者的无进展生存期。组合的安全性与单个药剂观察到的一致。这些结果支持使用atezolizumab联合铂类化疗作为转移性尿路上皮癌的潜在一线治疗选择。资金筹集Hoffmann-La Roche和Genentech。B组22例(6%),C组132例(34%)。A组50例(11%),B组21例(6%),B组27例(7%) C有不良事件,导致终止atezolizumab或安慰剂。解释作为铂金的一线治疗,将阿特珠单抗作为一线治疗可延长转移性尿路上皮癌患者的无进展生存期。组合的安全性与单个药剂观察到的一致。这些结果支持使用atezolizumab联合铂类化疗作为转移性尿路上皮癌的潜在一线治疗选择。资金筹集Hoffmann-La Roche和Genentech。C组中有27名患者(7%)出现不良事件,导致终止了atezolizumab或安慰剂的停用。解释将阿特珠单抗加到铂类化疗中作为一线治疗可延长转移性尿路上皮癌患者的无进展生存期。组合的安全性与单个药剂观察到的一致。这些结果支持使用atezolizumab联合铂类化疗作为转移性尿路上皮癌的潜在一线治疗选择。资金筹集Hoffmann-La Roche和Genentech。C组中有27名患者(7%)出现不良事件,导致停用了atezolizumab或安慰剂。解释作为铂金的一线治疗,将阿特珠单抗作为一线治疗可延长转移性尿路上皮癌患者的无进展生存期。组合的安全性与单个药剂观察到的一致。这些结果支持使用atezolizumab联合铂类化疗作为转移性尿路上皮癌的潜在一线治疗选择。资金筹集Hoffmann-La Roche和Genentech。组合的安全性与单个药剂观察到的一致。这些结果支持使用atezolizumab联合铂类化疗作为转移性尿路上皮癌的潜在一线治疗选择。资金筹集Hoffmann-La Roche和Genentech。组合的安全性与单个药剂观察到的一致。这些结果支持使用atezolizumab联合铂类化疗作为转移性尿路上皮癌的潜在一线治疗选择。资金筹集Hoffmann-La Roche和Genentech。
更新日期:2020-05-14
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