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[阿替利珠单抗(泰圣奇):在晚期或转移性膀胱癌中的活性、适应证及使用方式]

[Atezolizumab (Tecentriq): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma].

作者信息

Bernard-Tessier Alice, Bonnet Clément, Lavaud Pernelle, Gizzi Marco, Loriot Yohann, Massard Christophe

机构信息

University of Paris Sud, Gustave Roussy cancer campus, drug development department, 94805 Villejuif cedex, France; University of Paris Sud, Gustave Roussy cancer campus, department of medical oncology, 94805 Villejuif cedex, France.

Grand hôpital de Charleroi (GHdC), department of medical oncology, grand rue 3, 6000 Charleroi, Belgium.

出版信息

Bull Cancer. 2018 Feb;105(2):140-145. doi: 10.1016/j.bulcan.2017.10.030. Epub 2017 Dec 28.

Abstract

Treatments for patients with metastatic or advanced urothelial carcinomas on progression after first line chemotherapy or unfit for cisplatin are currently limited. Atezolizumab (Tecentriq) is a monoclonal antibody targeting PD-L1. The first of IMVIGOR 210 phase II trial (NCT02951767) investigated atezolizumab as front line treatment among 119 patients with metastatic urothelial cancer unfit for cisplatin. Response rate was 23% and median overall survival 15.9 months. The second cohort (NCT02108652) included 310 patients whose tumors were progressing after first line platinum-based chemotherapy. Response rate was 15% and median overall survival 7.9 months. Among patients with high PD-L1 expression on infiltrating immune cells (ICs), response rate was 26% and median overall survival 11 months. Atezolizumab was well-tolerated in both cohorts with 66% of treatment-related toxicities including 12% (cohort 1) and 7% (cohort 2) of grade 3-4 adverse events. These results led to an approval by the FDA in United States and the EMA in Europe. In France, atezolizumab was available through an early access agreement by the French National Agency for Medicines and Health Products (ANSM) for patients with metastatic or advanced urothelial carcinomas on progression after first line chemotherapy or unfit for cisplatin. So far, its avaibility in France within the EMA approval is pending its pricing.

摘要

对于一线化疗后病情进展或不适合使用顺铂的转移性或晚期尿路上皮癌患者,目前的治疗方法有限。阿替利珠单抗(泰圣奇)是一种靶向程序性死亡配体1(PD-L1)的单克隆抗体。IMVIGOR 210 II期试验(NCT02951767)的第一项研究调查了阿替利珠单抗作为一线治疗药物,用于119例不适合使用顺铂的转移性尿路上皮癌患者。缓解率为23%,中位总生存期为15.9个月。第二个队列(NCT02108652)纳入了310例一线铂类化疗后肿瘤进展的患者。缓解率为15%,中位总生存期为7.9个月。在浸润性免疫细胞(IC)上高表达PD-L1的患者中,缓解率为26%,中位总生存期为11个月。在两个队列中,阿替利珠单抗的耐受性良好,66%的治疗相关毒性包括12%(队列1)和7%(队列2)的3-4级不良事件。这些结果促使美国食品药品监督管理局(FDA)和欧洲药品管理局(EMA)批准了该药物。在法国,通过法国国家药品和健康产品管理局(ANSM)的早期获取协议,阿替利珠单抗可供一线化疗后病情进展或不适合使用顺铂的转移性或晚期尿路上皮癌患者使用。到目前为止,在法国,其在EMA批准范围内的可用性仍有待定价。

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