Safety and Efficacy of Pembrolizumab in Advanced, Programmed Death Ligand 1-Positive Cervical Cancer: Results From the Phase Ib KEYNOTE-028 Trial
Safety and Efficacy of Pembrolizumab in Advanced, Programmed Death Ligand 1-Positive Cervical Cancer: Results From the Phase Ib KEYNOTE-028 Trial
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DOI：
10.1200/jco.2017.74.5471
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发表时间：
2017-12-20
影响因子：
45.3
通讯作者：
Varga, Andrea
中科院分区：
文献类型：
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作者：
Frenel, Jean-Sebastien;Le Tourneau, Christophe;Varga, Andrea
KEYNOTE-028试验（ClinicalTrials.gov标识符：NCT 02054806）旨在评估pembrolizumab在20个程序性死亡配体1阳性晚期实体瘤队列中的安全性和有效性。在这里，我们提出的结果，从队列的患者与晚期cervicalcancer.MethodsPatients治疗帕博利珠单抗10 mg/kg，每2周长达24个月。前6个月每8周评估一次缓解，此后每12周评估一次。主要终点是研究者审查的实体瘤疗效评价标准（第1.1版）规定的总体缓解率。安全性是一个次要的endpoint.Results24例患者参加了宫颈癌队列。中位年龄为42岁（范围：26 - 62岁），22例患者（92%）既往接受过放射治疗，15例患者（63%）接受过二线或二线以上治疗，包括贝伐珠单抗（10/24例患者）治疗晚期疾病。数据截止时，中位随访时间为11.0个月（范围：1.3 - 32.2个月）。总体缓解率为17%（95% CI，5%-37%）; 4例患者（17%）获得了确认的部分缓解，3例患者（13%）病情稳定。达到部分缓解的4例患者的中位缓解持续时间为5.4个月（4.1至7.5个月）。18名患者（75%）发生了治疗相关不良事件（AE）;仅皮疹（n = 5; 21%）和发热（n = 4; 17%），发生率>= 10%。5例患者发生3级治疗相关AE。没有4级治疗相关的AE或死亡observed.ConclusionIn程序性死亡配体1阳性晚期宫颈癌患者，pembrolizumab表现出抗肿瘤活性，并表现出与其他肿瘤类型的安全性相一致。(c)2017年美国临床肿瘤学会
PurposeThe KEYNOTE-028 trial (ClinicalTrials.gov identifier: NCT02054806) was designed to assess the safety and efficacy of pembrolizumab in 20 programmed death ligand 1-positive, advanced solid tumor cohorts. Here, we present the results from the cohort of patients with advanced cervical cancer.MethodsPatients were treated with pembrolizumab 10 mg/kg every 2 weeks for up to 24 months. Response was assessed every 8 weeks for the first 6 months and every 12 weeks thereafter. The primary end point was overall response rate per Response Evaluation Criteria in Solid Tumors, version 1.1, by investigator review. Safety was a secondary end point.ResultsTwenty-four patients were enrolled in the cervical cancer cohort. The median age was 42 years (range, 26 to 62 years), 22 patients (92%) had received prior radiation therapy, and 15 patients (63%) had received two or more lines of therapy, including bevacizumab (10 of 24 patients), for advanced disease. At the data cutoff, median follow-up duration was 11.0 months (range, 1.3 to 32.2 months). Overall response rate was 17% (95% CI, 5% to 37%); four patients (17%) achieved a confirmed partial response, and three patients (13%) had stable disease. Median duration of response for the four patients who achieved a partial response was 5.4 months (4.1 to 7.5 months). Treatment related adverse events (AEs) were experienced by 18 patients (75%); only rash (n = 5; 21%) and pyrexia (n = 4; 17%) and occurred in >= 10% of patients. Five patients experienced grade 3 treatment-related AEs. No grade 4 treatment-related AEs or deaths were observed.ConclusionIn patients with programmed death ligand 1-positive advanced cervical cancer, pembrolizumab demonstrated antitumor activity and exhibited a safety profile consistent with that seen in other tumor types. (c) 2017 by American Society of Clinical Oncology