David J. Vaughn, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; Joaquim Bellmunt and Toni K. Choueiri, Dana-Farber Cancer Institute, Boston, MA; Yves Fradet, CHU de Québec-Université Laval, Quebec City, Quebec, Canada; Jae Lyun Lee, Asan Medical Center and University of Ulsan College of Medicine, Seoul, Republic of Korea; Lawrence Fong, University of California, San Francisco, San Francisco; David I. Quinn, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA; Nicholas J. Vogelzang, Comprehensive Cancer Centers of Nevada, Las Vegas, NV; Miguel A. Climent, Fundación Instituto Valenciano de Oncología, Valencia, Spain; Daniel P. Petrylak, Smilow Cancer Hospital, Yale University, New Haven, CT; Andrea Necchi, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori, Milan; Cora N. Sternberg, San Camillo and Forlanini Hospitals, Rome, Italy; Winald Gerritsen, Radboud University Medical Center, Nijmegen; Ronald de Wit, Erasmus University Medical Center Cancer Institute, Rotterdam, the Netherlands; Howard Gurney, Westmead Hospital and Macquarie University, Sydney, New South Wales, Australia; Stephane Culine, Hôpital Saint-Louis, Paris, France; Yabing Mai, Haojie Li, and Rodolfo F. Perini, Merk & Co., Inc., Kenilworth, NJ; and Dean F. Bajorin, Memorial Sloan Kettering Cancer Center, New York, NY.
J Clin Oncol. 2018 Jun 1;36(16):1579-1587. doi: 10.1200/JCO.2017.76.9562. Epub 2018 Mar 28.
Purpose In the phase III KEYNOTE-045 study ( ClinicalTrials.gov identifier: NCT02256436), pembrolizumab significantly prolonged overall survival compared with investigator's choice of chemotherapy in patients with previously treated advanced urothelial cancer. Here, we report the results of health-related quality-of-life (HRQoL) analyses from the KEYNOTE-045 trial. Patients and Methods Patients were randomly assigned 1:1 to pembrolizumab 200 mg or investigator's choice of docetaxel 75 mg/m, paclitaxel 175 mg/m, or vinflunine 320 mg/m administered intravenously every 3 weeks. Key prespecified HRQoL analyses were time to deterioration (TTD) and mean change from baseline to week 15 in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 global health status/quality-of-life score. Results Of 542 patients who were randomly assigned, 519 were included in HRQoL analyses (pembrolizumab, n = 266; chemotherapy, n = 253). HRQoL compliance was > 95% at baseline and approximately 88% at week 15 for both groups. Pembrolizumab prolonged TTD in global health status/quality-of-life score compared with chemotherapy (median, 3.5 months v 2.3 months; hazard ratio, 0.72; nominal one-sided P = .004). Mean (95% CI) change from baseline to week 15 in global health status/quality-of-life score was 0.69 (-2.40 to 3.77) with pembrolizumab and -8.36 (-11.84 to -4.89) with chemotherapy (mean difference, 9.05 points; 95% CI, 4.61 to 13.50; nominal two-sided P < .001). Conclusion Pembrolizumab prolonged TTD in HRQoL compared with chemotherapy. Patients who were treated with pembrolizumab had stable or improved global health status/quality of life, whereas those who were treated with investigator's choice of chemotherapy experienced declines in global health status/quality of life. Combined with efficacy and safety outcomes, these data support pembrolizumab as standard of care for patients with platinum-refractory advanced urothelial cancer.
目的 在 III 期 KEYNOTE-045 研究（ClinicalTrials.gov 标识符：NCT02256436）中，与研究者选择的化疗相比，帕博利珠单抗显著延长了先前治疗的晚期尿路上皮癌患者的总生存期。在此，我们报告 KEYNOTE-045 试验的健康相关生活质量（HRQoL）分析结果。
方法 患者按 1:1 随机分配至帕博利珠单抗 200mg 或研究者选择的多西他赛 75mg/m²、紫杉醇 175mg/m²或长春氟宁 320mg/m²，每 3 周静脉输注一次。主要预设的 HRQoL 分析是从基线到第 15 周时的恶化时间（TTD）和欧洲癌症研究与治疗组织生活质量问卷 C30 全球健康状况/生活质量评分的平均变化。
结果 在随机分配的 542 例患者中，519 例患者纳入 HRQoL 分析（帕博利珠单抗组 n = 266；化疗组 n = 253）。两组患者在基线和第 15 周时的 HRQoL 依从性均＞95%。与化疗相比，帕博利珠单抗延长了全球健康状况/生活质量评分的 TTD（中位数 3.5 个月比 2.3 个月；风险比 0.72；单侧名义 P =.004）。从基线到第 15 周时，全球健康状况/生活质量评分的平均（95%CI）变化分别为帕博利珠单抗组 0.69（-2.40 至 3.77）和化疗组-8.36（-11.84 至-4.89）（平均差值 9.05 分；95%CI，4.61 至 13.50；双侧名义 P＜.001）。
结论 与化疗相比，帕博利珠单抗延长了 HRQoL 的 TTD。接受帕博利珠单抗治疗的患者的整体健康状况/生活质量稳定或改善，而接受研究者选择的化疗的患者的整体健康状况/生活质量下降。这些数据结合疗效和安全性结果，支持帕博利珠单抗作为铂类难治性晚期尿路上皮癌患者的标准治疗方法。
