Department of Drug Development, Gustave Roussy Cancer Campus, Villejuif, France.
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Gynecol Oncol. 2019 Feb;152(2):243-250. doi: 10.1016/j.ygyno.2018.11.017. Epub 2018 Dec 3.
To evaluate safety, tolerability, and antitumor activity of pembrolizumab monotherapy in patients with programmed death ligand 1 (PD-L1)-expressing advanced ovarian cancer enrolled in the multicohort, phase Ib KEYNOTE-028 trial.
Key inclusion criteria were age ≥18 years; advanced ovarian epithelial, fallopian tube, or primary peritoneal carcinoma; failure of previous therapy; and tumor PD-L1 positivity. Patients received pembrolizumab (10 mg/kg every 2 weeks) for ≤24 months or until disease progression/intolerable toxicity. Tumor response was assessed per RECIST v1.1 (investigator review). Adverse events (AEs) were graded using CTCAE version 4.0. Primary end point was confirmed objective response rate (ORR) per RECIST v1.1 (investigator review); data cutoff date was February 20, 2017.
Twenty-six patients (median age, 57.5 years) with PD-L1-positive advanced metastatic ovarian cancer received pembrolizumab; 38.5% had metastatic disease, and 73.1% previously received ≥3 lines of therapy. Treatment-related AEs (TRAEs) occurred in 19 (73.1%) patients, most commonly arthralgia (19.2%), nausea (15.4%), and pruritus (15.4%). One grade 3 TRAE (increased plasma transaminase level) occurred. No deaths and no treatment discontinuations due to TRAEs occurred. After a median follow-up duration of 15.4 months, ORR was 11.5% (1 complete response, 2 partial responses); 7 patients (26.9%) achieved stable disease. Median progression-free and overall survival were 1.9 (95% CI, 1.8-3.5) and 13.8 (95% CI, 6.7-18.8) months, respectively.
Pembrolizumab conferred durable antitumor activity with manageable safety and toxicity in patients with advanced PD-L1-positive ovarian cancer and is under further investigation in an ongoing phase II trial, KEYNOTE-100.
评估在多队列、Ib 期 KEYNOTE-028 试验中，入组的程序性死亡配体 1（PD-L1）表达的晚期卵巢癌患者中，帕博利珠单抗单药治疗的安全性、耐受性和抗肿瘤活性。
主要纳入标准为年龄≥18 岁；晚期卵巢上皮、输卵管或原发性腹膜癌；先前治疗失败；肿瘤 PD-L1 阳性。患者接受帕博利珠单抗（10mg/kg，每 2 周 1 次）治疗，最长 24 个月或直至疾病进展/无法耐受毒性。根据 RECIST v1.1（研究者评估）评估肿瘤应答。使用 CTCAE 版本 4.0 分级不良事件（AE）。主要终点为根据 RECIST v1.1（研究者评估）确认的客观缓解率（ORR）；数据截止日期为 2017 年 2 月 20 日。
26 例 PD-L1 阳性的晚期转移性卵巢癌患者接受了帕博利珠单抗治疗；38.5%患者有转移性疾病，73.1%患者先前接受过≥3 线治疗。19 例（73.1%）患者发生了治疗相关的 AE（TRAEs），最常见的是关节痛（19.2%）、恶心（15.4%）和瘙痒（15.4%）。1 例（3.8%）发生 3 级 TRAE（血浆转氨酶升高）。无死亡和因 TRAE 而停药的情况发生。中位随访 15.4 个月后，ORR 为 11.5%（1 例完全缓解，2 例部分缓解）；7 例（26.9%）患者疾病稳定。中位无进展生存期和总生存期分别为 1.9（95%CI，1.8-3.5）和 13.8（95%CI，6.7-18.8）个月。
帕博利珠单抗在晚期 PD-L1 阳性卵巢癌患者中具有持久的抗肿瘤活性，且安全性和毒性可管理，正在一项正在进行的 II 期试验 KEYNOTE-100 中进行进一步研究。
