1 Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
2 Antoni van Leeuwenhoek Ziekenhuis, Amsterdam, the Netherlands.
J Clin Oncol. 2019 Jun 10;37(17):1470-1478. doi: 10.1200/JCO.18.01265. Epub 2019 Apr 3.
KEYNOTE-158 ( ClinicalTrials.gov identifier: NCT02628067) is a phase II basket study investigating the antitumor activity and safety of pembrolizumab in multiple cancer types. We present interim results from patients with previously treated advanced cervical cancer.
Patients received pembrolizumab 200 mg every 3 weeks for 2 years or until progression, intolerable toxicity, or physician or patient decision. Tumor imaging was performed every 9 weeks for the first 12 months and every 12 weeks thereafter. The primary end point was objective response rate (ORR), assessed per Response Evaluation Criteria in Solid Tumors (version 1.1) by independent central radiologic review. Safety was a secondary end point.
Ninety-eight patients were treated. Median age was 46.0 years (range, 24 to 75 years), and 65.3% of patients had Eastern Cooperative Oncology Group performance status of 1. Eighty-two patients (83.7%) had programmed death-ligand 1 (PD-L1)-positive tumors (combined positive score ≥ 1), 77 having previously received one or more lines of chemotherapy for recurrent or metastatic disease. Median follow-up was 10.2 months (range, 0.6 to 22.7 months). ORR was 12.2% (95% CI, 6.5% to 20.4%), with three complete and nine partial responses. All 12 responses were in patients with PD-L1-positive tumors, for an ORR of 14.6% (95% CI, 7.8% to 24.2%); 14.3% (95% CI, 7.4% to 24.1%) of these responses were in those who had received one or more lines of chemotherapy for recurrent or metastatic disease. Median duration of response was not reached (range, ≥ 3.7 to ≥ 18.6 months). Treatment-related adverse events occurred in 65.3% of patients, and the most common were hypothyroidism (10.2%), decreased appetite (9.2%), and fatigue (9.2%). Treatment-related grade 3 to 4 adverse events occurred in 12.2% of patients.
Pembrolizumab monotherapy demonstrated durable antitumor activity and manageable safety in patients with advanced cervical cancer. On the basis of these results, the US Food and Drug Administration granted accelerated approval of pembrolizumab for patients with advanced PD-L1-positive cervical cancer who experienced progression during or after chemotherapy.
KEYNOTE-158（ClinicalTrials.gov 标识符：NCT02628067）是一项针对多种癌症类型的帕博利珠单抗抗肿瘤活性和安全性的 II 期篮子研究。我们报告了先前接受过治疗的晚期宫颈癌患者的中期结果。
患者每 3 周接受 200mg 帕博利珠单抗治疗，持续 2 年或直至疾病进展、无法耐受毒性、医生或患者决定停药。在第 1 年的前 12 个月每 9 周进行一次肿瘤影像学检查，此后每 12 周进行一次。主要终点为独立中心放射学评估的实体瘤反应评估标准（版本 1.1）下的客观缓解率（ORR）。安全性是次要终点。
共治疗了 98 例患者。中位年龄为 46.0 岁（范围 24 至 75 岁），65.3%的患者 ECOG 表现状态为 1 分。82 例（83.7%）患者肿瘤 PD-L1 阳性（联合阳性评分≥1），77 例患者先前接受过一次或多次化疗用于治疗复发性或转移性疾病。中位随访时间为 10.2 个月（范围 0.6 至 22.7 个月）。ORR 为 12.2%（95%CI，6.5%至 20.4%），有 3 例完全缓解和 9 例部分缓解。所有 12 例缓解均发生在 PD-L1 阳性肿瘤患者中，ORR 为 14.6%（95%CI，7.8%至 24.2%）；14.3%（95%CI，7.4%至 24.1%）的缓解发生在先前接受过一次或多次化疗用于治疗复发性或转移性疾病的患者中。中位缓解持续时间未达到（范围，≥3.7 至≥18.6 个月）。65.3%的患者发生治疗相关不良事件，最常见的是甲状腺功能减退症（10.2%）、食欲下降（9.2%）和乏力（9.2%）。12.2%的患者发生 3 级或 4 级治疗相关不良事件。
帕博利珠单抗单药治疗在晚期宫颈癌患者中显示出持久的抗肿瘤活性和可管理的安全性。基于这些结果，美国食品和药物管理局批准了帕博利珠单抗用于治疗在化疗期间或之后疾病进展的晚期 PD-L1 阳性宫颈癌患者。
