Purpose The anti-programmed death-1 antibody pembrolizumab was evaluated in KEYNOTE-028, a multicohort, phase IB study of patients with programmed death ligand-1 (PD-L1)-positive advanced solid tumors. Results from the esophageal carcinoma cohort are reported herein. Patients and Methods Eligible patients with squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction in whom standard therapy failed and who had PD-L1-positive tumors received pembrolizumab 10 mg/kg every 2 weeks for up to 2 years or until confirmed disease progression or intolerable toxicity. Response was assessed every 8 weeks up to 6 months and every 12 weeks thereafter. Primary end points were safety and overall response rate, determined by investigator review per Response Evaluation Criteria in Solid Tumors (version 1.1). Results Among 83 patients with esophageal carcinoma and samples evaluable for PD-L1 expression, 37 (45%) had PD-L1-positive tumors, and 23 were enrolled. Median age was 65 years; 78% had squamous histology; and 87% received ≥ two prior therapies for advanced/metastatic disease. As of the data cutoff (February 20, 2017), median follow-up was 7 months (range, 1 to 33 months). Nine patients (39%) experienced treatment-related adverse events, most commonly decreased appetite, decreased lymphocyte count, generalized rash, and rash (two patients [9%] each). No grade 4 adverse events or deaths were attributed to pembrolizumab. Overall response rate was 30% (95% CI, 13% to 53%); median duration of response was 15 months (range, 6 to 26 months). A six-gene interferon-γ gene expression signature analysis suggested that delayed progression and increased response occur among pembrolizumab-treated patients with higher interferon-γ composite scores. Conclusion Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in patients with heavily pretreated, PD-L1-positive advanced esophageal carcinoma.

中文翻译：

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抗程序性死亡 1 抗体派姆单抗在晚期食管癌患者中的安全性和抗肿瘤活性

目的 抗程序性死亡 1 抗体派姆单抗在 KEYNOTE-028 中进行评估，KEYNOTE-028 是一项针对程序性死亡配体 1 (PD-L1) 阳性晚期实体瘤患者的多队列 IB 期研究。本文报告了食管癌队列的结果。患者和方法 标准治疗失败且患有 PD-L1 阳性肿瘤的鳞状细胞癌或食管或胃食管交界处腺癌符合条件的患者，每 2 周接受 10 mg/kg 帕博利珠单抗治疗长达 2 年或直至确认疾病进展或无法忍受的毒性。反应每 8 周评估一次，直至 6 个月，之后每 12 周评估一次。主要终点是安全性和总体反应率，由研究者根据实体瘤反应评估标准（1.1 版）审查确定。结果 在 83 名可评估 PD-L1 表达的食管癌患者中，37 名 (45%) 患有 PD-L1 阳性肿瘤，23 名被纳入研究。中位年龄为 65 岁；78% 有鳞状组织学；87% 接受了≥ 两种先前针对晚期/转移性疾病的治疗。截至数据截止日期（2017 年 2 月 20 日），中位随访时间为 7 个月（范围，1 至 33 个月）。9 名患者 (39%) 经历了与治疗相关的不良事件，最常见的是食欲下降、淋巴细胞计数减少、全身皮疹和皮疹（每名 2 名患者 [9%]）。没有 4 级不良事件或死亡归因于派姆单抗。总体反应率为 30%（95% CI，13% 至 53%）；中位反应持续时间为 15 个月（范围，6 至 26 个月）。一项六基因干扰素-γ 基因表达特征分析表明，在干扰素-γ 综合评分较高的帕博利珠单抗治疗患者中，进展延迟和反应增加。结论 Pembrolizumab 在经过大量预处理的 PD-L1 阳性晚期食管癌患者中表现出可控的毒性和持久的抗肿瘤活性。