Purpose To 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 Methods KEYNOTE-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. Results Twenty-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 a median follow-up of 20 months. ORR by central review was similar (26.3%). Drug-related adverse events that occurred in 15% or more 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. Conclusion Pembrolizumab demonstrated antitumor activity and a manageable safety profile in patients with RM-NPC.

中文翻译：

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派姆单抗在程序性死亡配体 1 阳性鼻咽癌患者中的安全性和抗肿瘤活性：KEYNOTE-028 研究的结果

目的 确定抗程序性死亡 1 受体单克隆抗体派姆单抗在表达程序性死亡配体 1 (PD-L1) 的复发性或转移性鼻咽癌 (RM-NPC) 患者中的安全性和抗肿瘤活性。患者和方法 KEYNOTE-028 (NCT02054806) 是一项非随机、多队列、Ib 期帕博利珠单抗试验，用于 PD-L1 阳性晚期实体瘤患者。NPC 队列的关键合格标准包括不可切除或转移性疾病、先前标准治疗失败以及 1% 或更多肿瘤细胞或肿瘤浸润淋巴细胞中的 PD-L1 表达。患者每 2 周接受一次 pembrolizumab 10 mg/kg，直至 2 年或直至疾病进展或出现不可接受的毒性。主要终点是每个研究者审查的客观反应率 (ORR)。根据实体瘤反应评估标准（RECIST；1.1 版）评估肿瘤反应，前 6 个月每 8 周评估一次，之后每 12 周评估一次。结果 27 名患者接受了 pembrolizumab。中位年龄为 52.0 岁（范围，18 至 68 岁）；92.6% 曾接受过 RM-NPC 的治疗；70.4% 接受过三种或三种以上的治疗。在中位随访 20 个月内，分别在 7 名和 14 名患者中观察到部分缓解和疾病稳定，ORR 为 25.9%（95% CI，11.1 至 46.3）。中央审查的 ORR 相似（26.3%）。发生在 15% 或更多患者中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%) 发生了≥3 级药物相关不良事件，并且有 1 例与药物相关的死亡（败血症）。截至数据截止（2016 年 6 月 20 日），两名患者仍在接受派姆单抗治疗。结论 Pembrolizumab 在 RM-NPC 患者中显示出抗肿瘤活性和可控的安全性。