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JCO：PD-L1抗体Durvalumab (MEDI4736)治疗晚期尿道上皮膀胱癌患者安全有效

2016年06月20日

编译：李淑娈

来源：桓兴医讯

目的（Purpose）

Durvalumab是一种与程序性细胞死亡配体-1(PD-L1)结合的人源性单克隆抗体，本研究旨在了解Durvalumab在晚期尿道上皮膀胱癌患者中的安全性、有效性以及PD-L1表达对临床疗效的影响。

To investigate the safety and efficacy of durvalumab, a human monoclonal antibody that binds programmed cell death ligand-1 (PD-L1), and the role of PD-L1 expression on clinical response in patients with advanced urothelial bladder cancer (UBC).

方法（Methods）

在不能手术或转移的实体瘤患者中正在进行一项多中心、开放标签的1/2期研究。我们在此报告来自尿道上皮膀胱癌扩展队列的结果。Durvalumab (MEDI4736，10mg/kg，每2周一次)，静脉注射，至12个月。主要终点是安全性，一项关键次要终点为客观缓解率（ORR）。对治疗前肿瘤活检结果进行探索性分析，确定PD-L1阳性情况，肿瘤细胞或浸润肿瘤的免疫细胞膜PD-1表达≥25%为PD-L1阳性。

A phase 1/2 multicenter, open-label study is being conducted in patients with inoperable or metastatic solid tumors. We report here the results from the UBC expansion cohort. Durvalumab (MEDI4736, 10 mg/kg every 2 weeks) was administered intravenously for up to 12 months. The primary end point was safety, and objective response rate (ORR, confirmed) was a key secondary end point. An exploratory analysis of pretreatment tumor biopsies led to defining PD-L1–positive as ≥ 25% of tumor cells or tumor-infiltrating immune cells expressing membrane PD-L1.

结果（Results）

共治疗61名患者（40名PD-1阳性、21名PD-1阴性）（中位随访期4.3个月），其中93.4%的患者既往接受过≥1种的晚期尿道上皮膀胱癌治疗方案。最常见的任何程度的治疗相关不良反应为疲乏（13.1%）、腹泻（9.8%）、食欲下降（8.2%）。3名患者（4.9%）出现3级治疗相关不良反应，没有4级或5级治疗相关不良反应，1名因治疗相关不良反应（急性肾功能损伤）而中断治疗。在42名可进行疗效评价的患者中，客观缓解率为31.0%（95%CI17.6-47.1），PD-L1阳性亚组为46.4% (95%CI27.5-66.1)，PD-L-1阴性亚组为0%(95%CI0.0-23.2)。治疗有反应的13名患者中12例持续缓解，现尚未达到持续缓解的中位时间（从4.1+至49.3+周）。

A total of 61 patients (40 PD-L1–positive, 21 PD-L1–negative), 93.4% of whom received one or more prior therapies for advanced disease, were treated (median duration of follow-up, 4.3 months). The most common treatment-related adverse events (AEs) of any grade were fatigue (13.1%), diarrhea (9.8%), and decreased appetite (8.2%). Grade 3 treatment-related AEs occurred in three patients (4.9%); there were no treatment-related grade 4 or 5 AEs. One treatment-related AE (acute kidney injury) resulted in treatment discontinuation. The ORR was 31.0% (95% CI, 17.6 to 47.1) in 42 response-evaluable patients, 46.4% (95% CI, 27.5 to 66.1) in the PD-L1–positive subgroup, and 0% (95% CI, 0.0 to 23.2) in the PD-L1–negative subgroup. Responses are ongoing in 12 of 13 responding patients, with median duration of response not yet reached (range, 4.1+ to 49.3+ weeks).

结论（Conclusion）

在许多既往进行过大量治疗、PD-L1阳性尿道上皮膀胱癌患者中，证实Durvalumab安全性控制，且临床疗效有意义。

Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1–positive patients with UBC, many of whom were heavily pretreated.

责任编辑：Dr.q