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CheckMate 650试验结果分析
作者:小柯机器人 发布时间:2020/9/12 22:13:44

美国德克萨斯大学MD安德森癌症中心Padmanee Sharma研究组取得一项新突破。他们利用诺沃单抗加依普利单抗治疗转移性去势抵抗性前列腺癌,对CheckMate 650试验中患者进行了初步分析。2020年9月10日,《癌细胞》杂志发表了这项成果。

他们报道了迄今为止在mCRPC中最大的抗CTLA-4和抗PD-1试验(诺沃单抗1 mg / kg依普利3 mg / kg; CheckMate 650,NCT02985957)。队列1(化疗前; n = 45)和队列2(化疗后; n = 45)的中位随访时间分别为11.9和13.5个月,客观缓解率为25%和10%,中位总生存率为19.0和15.2个月。

四个患者,每个队列中有两个完全缓解。探索性研究确定了潜在的反应生物标志物。约有42%–53%的患者发生了3–4级与治疗相关的不良事件,其中有4名导致治疗相关的死亡。因此,已经进行了剂量/时间表的修改。

据了解,转移性去势抵抗性前列腺癌(mCRPC)在免疫学上是“冷”的,并且由于肿瘤浸润性T细胞很少,因此主要抵抗免疫检查点疗法。依普利单抗(抗CTLA-4)或抗PD-1 / PD-L1单一疗法未能显示出明显的获益。尽管PD-1 / PD-L1途径在前列腺肿瘤中的表达最少,但他们先前证明PD-1 / PD-L1的表达作为补偿性抑制途径而增加,与依普利单抗诱导的肿瘤浸润T细胞的增加类似。

附:英文原文

Title: Nivolumab Plus Ipilimumab for Metastatic Castration-Resistant Prostate Cancer: Preliminary Analysis of Patients in the CheckMate 650 Trial

Author: Padmanee Sharma, Russell K. Pachynski, Vivek Narayan, Aude Fléchon, Gwenaelle Gravis, Matthew D. Galsky, Hakim Mahammedi, Akash Patnaik, Sumit K. Subudhi, Marika Ciprotti, Burcin Simsek, Abdel Saci, Yanhua Hu, G. Celine Han, Karim Fizazi

Issue&Volume: 2020-09-10

Abstract: Metastatic castration-resistant prostate cancer (mCRPC) is immunologically “cold”and predominantly resistant to immune checkpoint therapy due to few tumor-infiltratingT cells. Ipilimumab (anti-CTLA-4) or anti-PD-1/PD-L1 monotherapy failed to show asignificant benefit. Although the PD-1/PD-L1 pathway is minimally expressed in prostatetumors, we previously demonstrated that PD-1/PD-L1 expression increases as a compensatoryinhibitory pathway in parallel with an ipilimumab-induced increase in tumor-infiltratingT cells. Here, we report the largest trial to date in mCRPC with anti-CTLA-4 plusanti-PD-1 (nivolumab 1 mg/kg plus ipilimumab 3 mg/kg; CheckMate 650, NCT02985957).With median follow-ups of 11.9 and 13.5 months in cohorts 1 (pre-chemotherapy; n =45) and 2 (post-chemotherapy; n = 45), objective response rate was 25% and 10%, andmedian overall survival was 19.0 and 15.2 months, respectively. Four patients, twoin each cohort, had complete responses. Exploratory studies identify potential biomarkersof response. Grade 3–4 treatment-related adverse events have occurred in ~42%–53%of patients, with four treatment-related deaths. Therefore, dose/schedule modificationshave been implemented.

DOI: 10.1016/j.ccell.2020.08.007

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30418-9

期刊信息

Cancer Cell:《癌细胞》,创刊于2002年。隶属于细胞出版社,最新IF:23.916
官方网址:https://www.cell.com/cancer-cell/home
投稿链接:https://www.editorialmanager.com/cancer-cell/default.aspx