辅助性帕博利珠单抗对比观察用于肌层浸润性尿路上皮癌
Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma.
作者信息
Apolo Andrea B, Ballman Karla V, Sonpavde Guru, Berg Stephanie, Kim William Y, Parikh Rahul, Teo Min Yuen, Sweis Randy F, Geynisman Daniel M, Grivas Petros, Chatta Gurkamal, Reichert Zachery Roger, Kim Joseph W, Bilen Mehmet Asim, McGregor Bradley, Singh Parminder, Tripathi Abhishek, Cole Suzanne, Simon Nicholas, Niglio Scot, Ley Lisa, Cordes Lisa, Srinivas Sandy, Huang Jiaoti, Odegaard Meagan, Watt Colleen, Petrylak Daniel, Hoffman-Censits Jeannie, Wen Yujia, Hahn Olwen, Mitchell Cecilia, Tan Alan, Streicher Howard, Sharon Elad, Moon Helen, Woods Michael, Halabi Susan, Perez Burbano Gabriela, Morris Michael J, Rosenberg Jonathan E
机构信息
From the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda (A.B.A., N.S., S.N., L.L., L.C.), the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.H.-C.), and the Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Rockville (H.S., E.S.) - all in Maryland; the Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN (K.V.B., M.O., C.M., G.P.B.); AdventHealth Cancer Institute and the University of Central Florida, Orlando (G.S.); Dana-Farber/Harvard Cancer Center, Boston (S.B., B.M.); UNC Lineberger Comprehensive Cancer Center, Chapel Hill (W.Y.K.), and Duke University Medical Center and Duke Cancer Institute, Durham (J.H., S.H.) - both in North Carolina; the University of Kansas Cancer Center, Westwood (R.P.); Memorial Sloan Kettering Cancer Center, New York (M.Y.T., M.J.M., J.E.R.), and Roswell Park Comprehensive Cancer Center, Buffalo (G.C.) - both in New York; the University of Chicago Comprehensive Cancer Center, Chicago (R.F.S., C.W., Y.W., O.H.), and Loyola University Medical Center, Maywood (M.W.) - both in Illinois; the Alliance Protocol Operations Office, University of Chicago, Chicago (C.W., Y.W., O.H.); Fox Chase Cancer Center, Philadelphia (D.M.G.); Fred Hutchinson Cancer Center and the University of Washington, Seattle (P.G.); Rogel Cancer Center, University of Michigan, Ann Arbor (Z.R.R.); Yale Cancer Center, Yale School of Medicine, New Haven, CT (J.W.K., D.P.); Winship Cancer Institute, Emory University, Atlanta (M.A.B.); Mayo Clinic Comprehensive Cancer Center, Phoenix, AZ (P.S.); Oklahoma University Health Stephenson Cancer Center, Oklahoma City (A. Tripathi); University of Texas Southwestern Medical Center, Dallas (S.C.); Stanford University, Stanford (S.S.), and Kaiser Permanente Riverside Medical Center, Riverside (H.M.) - both in California; and Vanderbilt-Ingram Cancer Center, Nashville (A. Tan).
出版信息
N Engl J Med. 2025 Jan 2;392(1):45-55. doi: 10.1056/NEJMoa2401726. Epub 2024 Sep 15.
BACKGROUND
Muscle-invasive urothelial carcinoma is an aggressive disease with high rates of relapse. Whether pembrolizumab as adjuvant therapy would be effective in patients with high-risk muscle-invasive urothelial carcinoma after radical surgery is unknown.
METHODS
In this phase 3 trial, we randomly assigned patients, in a 1:1 ratio, to receive pembrolizumab at a dose of 200 mg every 3 weeks for 1 year or to undergo observation. Randomization was stratified according to pathological stage, centrally tested programmed death ligand 1 (PD-L1) status, and previous neoadjuvant chemotherapy. The coprimary end points were disease-free survival and overall survival in the intention-to-treat population. We considered the trial to be successful if either disease-free survival or overall survival was significantly longer with pembrolizumab than with observation.
RESULTS
A total of 702 patients underwent randomization; 354 were assigned to receive pembrolizumab, and 348 were assigned to observation. As of July 5, 2024, the median duration of follow-up for disease-free survival was 44.8 months. The median disease-free survival was 29.6 months (95% confidence interval [CI], 20.0 to 40.7) with pembrolizumab and 14.2 months (95% CI, 11.0 to 20.2) with observation (hazard ratio for disease progression or death, 0.73; 95% CI, 0.59 to 0.90; two-sided P = 0.003). Grade 3 or higher adverse events (regardless of attribution) occurred in 50.6% of the patients in the pembrolizumab group and in 31.6% of the patients in the observation group.
CONCLUSIONS
Among patients with high-risk muscle-invasive urothelial carcinoma after radical surgery, disease-free survival was significantly longer with adjuvant pembrolizumab than with observation. (Funded by the National Cancer Institute of the National Institutes of Health and others; Alliance A031501 AMBASSADOR ClinicalTrials.gov number, NCT03244384.).
背景
肌层浸润性尿路上皮癌是一种侵袭性疾病，复发率很高。帕博利珠单抗作为辅助治疗对高危肌层浸润性尿路上皮癌患者根治术后是否有效尚不清楚。
方法
在这项3期试验中，我们将患者按1:1的比例随机分配，一组每3周接受一次200mg帕博利珠单抗治疗，共1年，另一组进行观察。随机分组根据病理分期、中心检测的程序性死亡配体1（PD-L1）状态和既往新辅助化疗情况进行分层。共同主要终点是意向性治疗人群的无病生存期和总生存期。如果帕博利珠单抗组的无病生存期或总生存期显著长于观察组，我们认为该试验成功。
结果
共有702例患者进行了随机分组；354例被分配接受帕博利珠单抗治疗，348例被分配接受观察。截至2024年7月5日，无病生存期的中位随访时间为44.8个月。帕博利珠单抗组的中位无病生存期为29.6个月（95%置信区间[CI]，20.0至40.7），观察组为14.2个月（95%CI，11.0至20.2）（疾病进展或死亡的风险比为0.73；95%CI，0.59至0.90；双侧P = 0.003）。帕博利珠单抗组50.6%的患者发生3级或更高等级的不良事件（无论归因如何），观察组为31.6%。
结论
在根治术后的高危肌层浸润性尿路上皮癌患者中，辅助使用帕博利珠单抗的无病生存期显著长于观察。（由美国国立卫生研究院国家癌症研究所及其他机构资助；联盟A031501大使临床试验注册号，NCT03244384。）
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