Safety and Antitumor Activity of the Anti-Programmed Death-1 Antibody Pembrolizumab in Patients With Advanced Esophageal Carcinoma
Safety and Antitumor Activity of the Anti-Programmed Death-1 Antibody Pembrolizumab in Patients With Advanced Esophageal Carcinoma
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DOI：
10.1200/jco.2017.74.9846
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发表时间：
2018-01-01
影响因子：
45.3
通讯作者：
Bennouna, Jaafar
中科院分区：
文献类型：
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作者：
Doi, Toshihiko;Piha-Paul, Sarina A.;Bennouna, Jaafar
目的抗程序性死亡 1 抗体派姆单抗在 KEYNOTE-028 中进行了评估，这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 IB 期多队列研究。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 阳性肿瘤的食管或胃食管交界处鳞状细胞癌或腺癌的合格患者每 2 周接受 10 mg/kg 的派姆单抗治疗，持续长达 2 年或直到确认疾病进展或出现无法耐受的毒性。每 8 周至 6 个月评估一次疗效，此后每 12 周评估一次。主要终点是安全性和总体缓解率，由研究者根据实体瘤疗效评估标准（1.1 版）审查确定。结果 在 83 名食管癌患者和可评估 PD-L1 表达的样本中，37 例 (45%) 患有 PD-L1 阳性肿瘤，其中 23 例入组。中位年龄为 65 岁； 78% 具有鳞状组织学； 87% 的患者接受过两种以上的晚期/转移性疾病治疗。截至数据截止（2017 年 2 月 20 日），中位随访时间为 7 个月（范围：1 至 33 个月）。九名患者 (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（每人两名患者 [9%]）。没有 4 级不良事件或死亡归因于派姆单抗。总体缓解率为30%（95% CI，13%至53%）；中位缓解持续时间为 15 个月（范围为 6 至 26 个月）。六基因干扰素-g 基因表达特征分析表明，在干扰素-g 综合评分较高的接受派姆单抗治疗的患者中，进展延迟且反应增加。 结论 在经过大量预处理的 PD-L1 阳性晚期食管癌患者中，派姆单抗显示出可控的毒性和持久的抗肿瘤活性。 (c) 2017 年美国临床肿瘤学会
PurposeThe 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 MethodsEligible patients with squamous cell carcinoma or adenocarcinoma of the esophagus or gastro-esophageal 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).ResultsAmong 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, mostcommonly 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 15months (range, 6 to 26 months). A six-gene interferon-g gene expression signature analysis suggested that delayed progression and increased response occur among pembrolizumab-treated patients with higher interferon-g composite scores.ConclusionPembrolizumab demonstrated manageable toxicity and durable antitumor activity in patients with heavily pretreated, PD-L1-positive advanced esophageal carcinoma. (c) 2017 by American Society of Clinical Oncology