Safety and Antitumor Activity of Pembrolizumab in Advanced Programmed Death Ligand 1-Positive Endometrial Cancer: Results From the KEYNOTE-028 Study
Safety and Antitumor Activity of Pembrolizumab in Advanced Programmed Death Ligand 1-Positive Endometrial Cancer: Results From the KEYNOTE-028 Study
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DOI：
10.1200/jco.2017.72.5952
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发表时间：
2017-08-01
影响因子：
45.3
通讯作者：
Soria, Jean-Charles
中科院分区：
文献类型：
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作者：
Ott, Patrick A.;Bang, Yung-Jue;Soria, Jean-Charles
多队列Ib期KEYNOTE-028（NCT 02054806）研究旨在评估Pembrolizumab（一种抗程序性死亡1单克隆抗体）在程序性死亡配体1（PD-L1）阳性晚期实体瘤患者中的安全性和疗效。结果从先进的子宫内膜癌队列reported.Patients和MethodsFemale患者局部晚期或转移性PD-L1阳性子宫内膜癌谁经历了标准治疗后的进展是合格的。患者接受帕博利珠单抗10 mg/kg，每2周一次，持续长达24个月或直至疾病进展或不可接受的毒性。主要疗效终点为RECIST（1.1版）客观缓解率。次要终点包括安全性、缓解持续时间（DOR）、无进展生存期和总生存期。结果75例患者中，PD-L1阳性36例（48.0%），入组24例（32.0%）。这24例患者中有15例（62.5%）既往至少接受过2线晚期疾病治疗。3例患者（13.0%）达到了确认的部分缓解（95% CI，2.8%-33.6%）;未达到中位DOR。2例患者仍在接受治疗，并在数据截止时显示持续缓解。另外3例患者（13.0%）达到疾病稳定，中位持续时间为24.6周。1例达到部分缓解的患者存在聚合酶E突变。13名患者（54.2%）发生了治疗相关不良事件（AE），其中疲乏（20.8%）、瘙痒（16.7%）、发热（12.5%）和食欲下降（12.5%）发生在≥ 10%的患者中。4例患者报告了3级治疗相关AE。没有病人经历了4级AE，没有病人停止治疗，因为AE.ConclusionPembrolizumab表现出良好的安全性和持久的抗肿瘤活性，在一个亚组的患者进行了大量的预处理晚期PD-L1阳性子宫内膜癌。(C)2017年美国临床肿瘤学会
PurposeThe multicohort phase Ib KEYNOTE-028 (NCT02054806) study was designed to evaluate the safety and efficacy of pembrolizumab, an anti-programmed death 1 monoclonal antibody, in patients with programmed death ligand 1 (PD-L1) -positive advanced solid tumors. The results from the advanced endometrial cancer cohort are reported.Patients and MethodsFemale patients with locally advanced or metastatic PD-L1-positive endometrial cancer who had experienced progression after standard therapy were eligible. Patients received pembrolizumab 10 mg/kg every 2 weeks for up to 24 months or until progression or unacceptable toxicity. Primary efficacy end point was objective response rate by RECIST (version 1.1). Secondary end points included safety, duration of response (DOR), progression-free survival, and overall survival. The data cutoff was February 17, 2016.ResultsOf 75 patients screened, 36 (48.0%) had PD-L1-positive tumors, and 24 (32.0%) were enrolled. Fifteen (62.5%) of these 24 patients had received at least two previous lines of therapy for advanced disease. Three patients (13.0%) achieved confirmed partial response (95% CI, 2.8% to 33.6%); the median DOR was not reached. Two patients were still receiving treatment and exhibiting continued response at time of data cutoff. Three additional patients (13.0%) achieved stable disease, with a median duration of 24.6 weeks. One patient who achieved partial response had a polymerase E mutation. Thirteen patients (54.2%) experienced treatment-related adverse events (AEs), with fatigue (20.8%), pruritus (16.7%), pyrexia (12.5%), and decreased appetite (12.5%) occurring in >= 10% of patients. Grade 3 treatment-related AEs were reported in four patients. No patient experienced a grade 4 AE, and no patient discontinued treatment because of an AE.ConclusionPembrolizumab demonstrated a favorable safety profile and durable antitumor activity in a subgroup of patients with heavily pretreated advanced PD-L1-positive endometrial cancer. (C) 2017 by American Society of Clinical Oncology