Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study
Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study
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DOI：
10.1200/jco.18.01265
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发表时间：
2019-06-10
影响因子：
45.3
通讯作者：
Leary, Alexandra
中科院分区：
文献类型：
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作者：
Chung, Hyun Cheol;Ros, Willeke;Leary, Alexandra
KEYNOTE-158 （ClinicalTrials.gov标识号：NCT02628067）是一项II期一揽子研究，旨在研究派姆单抗在多种癌症类型中的抗肿瘤活性和安全性。我们报告了先前治疗过的晚期宫颈癌患者的中期结果。患者和方法患者每3周接受200mg派姆单抗治疗2年或直到病情进展、无法忍受的毒性或医生或患者的决定。肿瘤成像在前12个月每9周进行一次，此后每12周进行一次。主要终点是客观缓解率（ORR），通过独立的中心放射学审查，根据实体瘤反应评价标准（1.1版）进行评估。安全性是次要的终点。结果治疗98例。中位年龄46.0岁（范围24 ~ 75岁），65.3%的患者东部肿瘤合作组表现状态为1。82例（83.7%）患者为程序性死亡-配体1 （PD-L1）阳性肿瘤（联合阳性评分>= 1），77例既往因复发或转移性疾病接受过一种或多种化疗。中位随访时间为10.2个月（0.6 ~ 22.7个月）。ORR为12.2% (95% CI, 6.5% - 20.4%)， 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%）的缓解发生在因复发或转移性疾病接受过一种或多种化疗的患者中。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（10.2%）、食欲下降（9.2%）和疲劳（9.2%）。12.2%的患者发生与治疗相关的3 - 4级不良事件。结论派姆单抗单药治疗晚期宫颈癌具有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加速批准了pembrolizumab用于化疗期间或化疗后进展的晚期pd - l1阳性宫颈癌患者。(C) 2019由美国临床肿瘤学会批准
PURPOSE 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 AND METHODS 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.RESULTS 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.CONCLUSION 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. (C) 2019 by American Society of Clinical Oncology