Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1-Positive Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study
Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1-Positive Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study
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DOI：
10.1200/jco.2017.73.3675
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发表时间：
2017-12-20
影响因子：
45.3
通讯作者：
Hansen, Aaron R.
中科院分区：
文献类型：
--
作者：
Hsu, Chiun;Lee, Se-Hoon;Hansen, Aaron R.
目的
确定抗程序性死亡1受体单克隆抗体帕博利珠单抗在表达程序性死亡配体1（PD - L1）的复发或转移性鼻咽癌（RM - NPC）患者中的安全性和抗肿瘤活性。
患者与方法
KEYNOTE - 028（NCT02054806）是一项针对PD - L1阳性晚期实体瘤患者的帕博利珠单抗非随机、多队列、Ib期试验。鼻咽癌队列的关键入选标准包括不可切除或转移性疾病、既往标准治疗失败以及肿瘤细胞或肿瘤浸润淋巴细胞中PD - L1表达≥1%。患者每2周接受10mg/kg帕博利珠单抗治疗，最长2年，或直至疾病进展或出现不可接受的毒性。主要终点是研究者评估的客观缓解率（ORR）。在最初6个月每8周根据实体瘤疗效评价标准（RECIST；1.1版）评估肿瘤反应，之后每12周评估一次。
结果
27名患者接受了帕博利珠单抗治疗。中位年龄为52.0岁（范围，18 - 68岁）；92.6%的患者既往接受过RM - NPC治疗；70.4%的患者接受过三种或更多种治疗。分别有7名和14名患者观察到部分缓解和疾病稳定，在中位随访20个月时客观缓解率为25.9%（95%置信区间，11.1 - 46.3）。中心评估的客观缓解率相似（26.3%）。15%或更多患者发生的药物相关不良事件包括皮疹（25.9%）、瘙痒（25.9%）、疼痛（22.2%）、甲状腺功能减退（18.5%）和疲劳（18.5%）。8名患者（29.6%）发生≥3级药物相关不良事件，并有1例药物相关死亡（败血症）。截至数据截止日期（2016年6月20日），2名患者仍在接受帕博利珠单抗治疗。
结论
帕博利珠单抗在RM - NPC患者中显示出抗肿瘤活性和可控的安全性。（c）2017年美国临床肿瘤学会
PurposeTo establish the safety profile and antitumor activity of the anti-programmed death 1 receptor monoclonal antibody, pembrolizumab, in patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) that expressed programmed death-ligand 1 (PD-L1).Patients and MethodsKEYNOTE-028 (NCT02054806) is a nonrandomized, multicohort, phase Ib trial of pembrolizumab in patients with PD-L1-positive advanced solid tumors. Key eligibility criteria for the NPC cohort included unresectable or metastatic disease, failure on prior standard therapy, and PD-L1 expression in 1% or more of tumor cells or tumor-infiltrating lymphocytes. Patients received pembrolizumab 10 mg/kg every 2 weeks up to 2 years or until disease progression or unacceptable toxicity. Primary end point was objective response rate (ORR) per investigator review. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) every 8 weeks for the first 6 months and every 12 weeks thereafter.ResultsTwenty-seven patients received pembrolizumab. Median age was 52.0 years (range, 18 to 68 years); 92.6% received prior therapies for RM-NPC; 70.4% had received three or more therapies. Partial response and stable disease were observed in seven and 14 patients, respectively, for an ORR of 25.9%(95% CI, 11.1 to 46.3) over amedian follow-up of 20months. ORR by central reviewwas similar (26.3%). Drug-related adverse events that occurred in 15% ormore of patients included rash (25.9%), pruritus (25.9%), pain (22.2%), hypothyroidism (18.5%), and fatigue (18.5%). Grade >= 3 drug-related adverse events occurred in eight patients (29.6%), and there was one drug-related death (sepsis). As of the data cutoff (June 20, 2016), two patients remained on pembrolizumab treatment.ConclusionPembrolizumab demonstrated antitumor activity and amanageable safety profile in patients with RM-NPC. (c) 2017 by American Society of Clinical Oncology