Nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients with advanced solid tumors: Survival and long-term safety in a phase I trial.
Nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients with advanced solid tumors: Survival and long-term safety in a phase I trial.
复制标题
纳武单抗（抗 PD-1；BMS-936558；ONO-4538）治疗晚期实体瘤患者：I 期试验中的生存率和长期安全性。
DOI：
--
复制
发表时间：
2013
期刊：
影响因子：
--
通讯作者：
F. Hodi
中科院分区：
文献类型：
--
作者：
S. Topalian;M. Sznol;J. Brahmer;David F. McDermott;David C. Smith;S. Gettinger;J. Taube;Charles G. Drake;Drew M. Pardoll;J. Powderly;Richard D. Carvajal;J. Sosman;Michael B Atkins;S. Antonia;D. Spigel;Donald P. Lawrence;G. Kollia;A. Gupta;J. Wigginton;F. Hodi
背景：阻断程序性死亡-1(PD-1)是一种由活化的T细胞表达的共抑制受体，可以克服免疫抵抗并介导肿瘤的消退(Topian等人，NEJM 2012)。在这里，我们介绍了尼伏卢单抗(一种PD-1阻断单抗)在晚期实体瘤患者(PTS)I期研究中的长期安全性和有效性。方法：2008年至2012年间入选的受试者在剂量递增和/或队列扩大期间接受尼伏单抗(0.1mg10 mg/kg静脉滴注，q2w)治疗。在每个4次剂量周期后，用RECIST 1.0评估肿瘤。PTS接受了12个周期的≤，直到不可接受的毒性、确认的进展或CR。结果：共治疗非小细胞肺癌127例，黑色素瘤107例，肾细胞癌34例，结直肠癌19例，前列腺癌17例。在MEL、非小细胞肺癌和肾癌中观察到持久的OR(CR/PR)(表)；在54名接受≥1年随访的应答者中，28人持续了≥1年。在这些重度预处理的患者中，中位OS(47%，有3-5个既往系统性疾病史).
3002^ Background: Blockade of programmed death-1 (PD-1), a co-inhibitory receptor expressed by activated T cells, can overcome immune resistance and mediate tumor regression (Topalian et al., NEJM 2012). Here we present long-term safety and efficacy outcomes from a phase I study of nivolumab, a PD-1 blocking mAb, in patients (pts) with advanced solid tumors. Methods: Pts enrolled between 2008-2012 received nivolumab (0.1−10 mg/kg IV Q2W) during dose escalation and/or cohort expansion. Tumors were assessed by RECIST 1.0 after each 4-dose cycle. Pts received ≤12 cycles until unacceptable toxicity, confirmed progression, or CR. Results: 304 pts with non-small cell lung cancer (NSCLC, n=127, squamous and nonsquamous), melanoma (MEL, n=107), renal cell (RCC, n=34), colorectal (n=19) or prostate cancer (n=17) were treated. Durable ORs (CR/PR) were observed in MEL, NSCLC and RCC (Table); in 54 responders with ≥1 yr follow-up, 28 lasted ≥1 yr. Median OS in these heavily pretreated pts (47% with 3-5 prior systemic...