小柯机器人

美国德克萨斯大学MD安德森癌症中心Padmanee Sharma、Jianjun Gao等研究人员合作发现，新辅助药物PD-L1加CTLA-4阻断可用于治疗不符合顺铂治疗的可手术性高危尿路上皮癌。这一研究成果于2020年10月12日在线发表在国际学术期刊《自然—医学》上。

研究人员报道了首例先天性新辅助佐剂试验（NCT02812420）与抗PD-L1（durvalumab）加上抗CTLA-4（tremelimumab）在不符合顺铂治疗的患者中被鉴定为所有肿瘤均具有高风险特征（n=28）。高风险特征由肿块大、组织学变异、淋巴血管浸润、肾积水和/或高级别上呼吸道疾病定义。主要终点是安全性，研究人员观察到28例≥3级免疫相关不良事件的患者中有6例（21％），包括无症状实验室异常（n=4）、肝炎和结肠炎（n=2）。研究人员还观察到58％完成手术的患者病理完全缓解率为37.5％，降级至pT1或更低（n=24）。

总而言之，研究人员提供了新辅助抗PD-L1联合抗CTLA-4组合的初步安全性、疗效和生物标志物数据，从而保证了局部尿路上皮癌患者尤其是顺铂不适合高危患者的安全性，这类人群目前尚无既定的新辅助治疗护理标准。

据了解，免疫检查点疗法在局部尿路上皮癌的新辅助治疗中被测试，一项研究报告了接受抗PD-L1单药治疗的不符合顺铂标准的患者数据。该研究报告称，具有肿块肿瘤的患者，其已知的高风险特征被定义为大于临床T2疾病，患者反应较少，病理完全反应率为17％。

附：英文原文

Title: Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma

Author: Jianjun Gao, Neema Navai, Omar Alhalabi, Arlene Siefker-Radtke, Matthew T. Campbell, Rebecca Slack Tidwell, Charles C. Guo, Ashish M. Kamat, Surena F. Matin, John C. Araujo, Amishi Y. Shah, Pavlos Msaouel, Paul Corn, Jianbo Wang, John N. Papadopoulos, Shalini S. Yadav, Jorge M. Blando, Fei Duan, Sreyashi Basu, Wenbin Liu, Yu Shen, Yuwei Zhang, Marc Daniel Macaluso, Ying Wang, Jianfeng Chen, Jianhua Zhang, Andrew Futreal, Colin Dinney, James P. Allison, Sangeeta Goswami, Padmanee Sharma

Issue&Volume: 2020-10-12

Abstract: Immune checkpoint therapy is being tested in the neoadjuvant setting for patients with localized urothelial carcinoma1,2, with one study reporting data in cisplatin-ineligible patients who received anti-PD-L1 monotherapy2. The study reported that patients with bulky tumors, a known high-risk feature defined as greater than clinical T2 disease, had fewer responses, with pathological complete response rate of 17%2. Here we report on the first pilot combination neoadjuvant trial (NCT02812420) with anti-PD-L1 (durvalumab) plus anti-CTLA-4 (tremelimumab) in cisplatin-ineligible patients, with all tumors identified as having high-risk features (n=28). High-risk features were defined by bulky tumors, variant histology, lymphovascular invasion, hydronephrosis and/or high-grade upper tract disease3,4,5. The primary endpoint was safety and we observed 6 of 28 patients (21%) with grade ≥3 immune-related adverse events, consisting of asymptomatic laboratory abnormalities (n=4), hepatitis and colitis (n=2). We also observed pathological complete response of 37.5% and downstaging to pT1 or less in 58% of patients who completed surgery (n=24). In summary, we provide initial safety, efficacy and biomarker data with neoadjuvant combination anti-PD-L1 plus anti-CTLA-4, which warrants further development for patients with localized urothelial carcinoma, especially cisplatin-ineligible patients with high-risk features who do not currently have an established standard-of-care neoadjuvant treatment.

DOI: 10.1038/s41591-020-1086-y

Source: https://www.nature.com/articles/s41591-020-1086-y

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
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投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex