Patrick A. Ott, Dana-Farber Cancer Institute, Boston, MA; Michael J. Pishvaian, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC; Hope S. Rugo, University of California San Francisco, San Francisco, CA; Igor Puzanov, Roswell Park Cancer Institute, Buffalo, NY; Janice M. Mehnert, Rutgers Cancer Institute of New Jersey, New Brunswick; Marion Carrigan, Sanatan Saraf, and Mei Chen, Merck, Kenilworth, NJ; Yung-Jue Bang, Seoul National University College of Medicine, Seoul, Republic of Korea; Dominique Berton-Rigaud, Institut de Cancérologie de l'Ouest Centre René Gauducheau, Saint-Herblain; Jean-Charles Soria, Gustave Roussy and University Paris-Sud, Villejuif, France; Elena Elez, Vall d'Hebron Institute of Oncology, Barcelona, Spain; Kyaw L. Aung, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; and Juanita Lopez, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, United Kingdom.
J Clin Oncol. 2017 Aug 1;35(22):2535-2541. doi: 10.1200/JCO.2017.72.5952. Epub 2017 May 10.
Purpose The 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 Methods Female 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. Results Of 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. Conclusion Pembrolizumab demonstrated a favorable safety profile and durable antitumor activity in a subgroup of patients with heavily pretreated advanced PD-L1-positive endometrial cancer.
多队列 Ib 期 KEYNOTE-028（NCT02054806）研究旨在评估抗程序性死亡 1 单克隆抗体 pembrolizumab 在 PD-L1（程序性死亡配体 1）阳性晚期实体瘤患者中的安全性和疗效。报告了晚期子宫内膜癌队列的结果。
符合条件的患者为接受标准治疗后进展的局部晚期或转移性 PD-L1 阳性子宫内膜癌的女性患者。患者接受 pembrolizumab 10 mg/kg，每 2 周一次，最多 24 个月或直至疾病进展或出现不可接受的毒性。主要疗效终点为 RECIST（版本 1.1）评估的客观缓解率。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。数据截止日期为 2016 年 2 月 17 日。
在筛选的 75 名患者中，36 名（48.0%）患者肿瘤 PD-L1 阳性，24 名（32.0%）患者入组。这 24 名患者中，15 名（62.5%）患者在接受至少两种晚期疾病的治疗方案。3 名患者（13.0%）获得了确认的部分缓解（95%CI，2.8%至 33.6%）；中位 DOR 未达到。两名患者仍在接受治疗，并在数据截止时持续缓解。另外 3 名患者（13.0%）获得了疾病稳定，中位持续时间为 24.6 周。1 名获得部分缓解的患者存在聚合酶 E 突变。13 名患者（54.2%）发生了治疗相关的不良事件（AE），疲劳（20.8%）、瘙痒（16.7%）、发热（12.5%）和食欲下降（12.5%）在≥10%的患者中出现。4 名患者出现了 3 级治疗相关 AE。没有患者出现 4 级 AE，也没有患者因 AE 而停止治疗。
在先前治疗过的晚期 PD-L1 阳性子宫内膜癌患者亚组中，pembrolizumab 显示出良好的安全性和持久的抗肿瘤活性。
