Cemiplimab阻断PD-1治疗晚期皮肤鳞状细胞癌 - NEJM医学前沿
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Cemiplimab阻断PD-1治疗晚期皮肤鳞状细胞癌
PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma


Michael R. Migden ... 肿瘤 呼吸系统疾病 • 2018.07.26
相关阅读
• PD-1检查点通路的分子和生化特征 • 抗PD-1抗体在癌症治疗中的安全性、有效性和免疫的相关性

摘要


背景

尚无批准用于治疗晚期皮肤鳞状细胞癌的全身疗法。这种癌症用免疫疗法治疗可能缓解,因为肿瘤的突变负荷高,且疾病风险与免疫抑制存在强相关性。在cemiplimab 1期研究的剂量递增部分,在转移性皮肤鳞状细胞癌患者中观察到深且持久的缓解。

 

方法

我们报告局部晚期或转移性皮肤鳞状细胞癌患者扩展队列的cemiplimab 1期研究结果,以及转移性皮肤鳞状细胞癌患者队列(转移性疾病队列)的关键性2期研究结果。在两项研究中,患者每2周接受1次cemiplimab(3 mg/kg体重)静脉内给药,随后每8周评估1次缓解情况。在2期研究中,主要终点为通过独立集中审查评估的缓解率。

 

结果

在1期研究的扩展队列中,在26例患者中的13例(50%;95%置信区间[CI],30%~70%)观察到接受cemiplimab有缓解。在2期研究的转移性疾病队列中,在59例中的28例(47%;95% CI,34%~61%)观察到缓解。在2期研究的转移性疾病队列中,中位随访时间为7.9个月。在有缓解的28例患者中,57%的缓解持续时间超过6个月,在数据截止时,82%继续有缓解,并继续接受cemiplimab治疗。2期研究转移性疾病队列中至少15%患者出现的不良事件包括腹泻、疲劳、恶心、便秘和皮疹;7%的患者因不良事件终止治疗。

 

结论

在晚期皮肤鳞状细胞癌患者中,cemiplimab在约一半的患者中引起了缓解,并且与使用免疫检查点抑制剂时常发生的不良事件相关(由再生元制药[Regeneron Pharmaceuticals]和赛诺菲资助;在ClinicalTrials.gov注册号为NCT02383212和NCT02760498)。





作者信息

Michael R. Migden, M.D., Danny Rischin, M.D., Chrysalyne D. Schmults, M.D., Alexander Guminski, M.D., Ph.D., Axel Hauschild, M.D., Karl D. Lewis, M.D., Christine H. Chung, M.D., Leonel Hernandez-Aya, M.D., Annette M. Lim, M.D., Ph.D., Anne Lynn S. Chang, M.D., Guilherme Rabinowits, M.D., Alesha A. Thai, M.D., Lara A. Dunn, M.D., Brett G.M. Hughes, M.D., Nikhil I. Khushalani, M.D., Badri Modi, M.D., Dirk Schadendorf, M.D., Bo Gao, Ph.D., Frank Seebach, M.D., Siyu Li, Ph.D., Jingjin Li, Ph.D., Melissa Mathias, M.D., Jocelyn Booth, M.B.A., Kosalai Mohan, Ph.D., Elizabeth Stankevich, B.S., Hani M. Babiker, M.D., Irene Brana, M.D., Ph.D., Marta Gil-Martin, M.D., Jade Homsi, M.D., Melissa L. Johnson, M.D., Victor Moreno, M.D., Ph.D., Jiaxin Niu, M.D., Ph.D., Taofeek K. Owonikoko, M.D., Ph.D., Kyriakos P. Papadopoulos, M.D., George D. Yancopoulos, M.D., Ph.D., Israel Lowy, M.D., Ph.D., and Matthew G. Fury, M.D., Ph.D.
From the Departments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston (M.R.M.), and South Texas Accelerated Research Therapeutics (START), San Antonio (K.P.P.) — both in Texas; the Department of Medical Oncology, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, VIC (D.R., A.A.T.), the Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, VIC (A.G.), the Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, WA (A.M.L.), and Royal Brisbane and Women’s Hospital and University of Queensland, Brisbane (B.G.M.H.) — all in Australia; the Department of Dermatology, Brigham and Women’s Hospital (C.D.S.), the Department of Dermatology, Harvard Medical School (C.D.S.), and the Department of Medical Oncology, Dana–Farber Cancer Institute (G.R.) — all in Boston; Schleswig-Holstein University Hospital, Kiel (A.H.), and University Hospital Essen, Essen and German Cancer Consortium, Essen (D.S.) — both in Germany; University of Colorado Denver, School of Medicine, Aurora (K.D.L.); the Departments of Head and Neck–Endocrine Oncology (C.H.C.) and Cutaneous Oncology (N.I.K.), H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; the Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis (L.H.-A.); the Department of Dermatology, Stanford University School of Medicine, Redwood City (A.L.S.C.), and the Division of Dermatology, City of Hope, Duarte (B.M.) — both in California; the Department of Medicine, Head and Neck Medical Oncology, Memorial Sloan Kettering Cancer Center, New York (L.A.D.), and Regeneron Pharmaceuticals, Tarrytown (F.S., M.M., K.M., G.D.Y., I.L., M.G.F.) — both in New York; Regeneron Pharmaceuticals, Basking Ridge, NJ (B.G., S.L., J.L., J.B., E.S.); University of Arizona Cancer Center, Tucson (H.M.B.), and Banner MD Anderson Cancer (J.H.) and the Department of Medical Oncology, Banner MD Anderson Cancer Center (J.N.), Gilbert — all in Arizona; Medical Oncology Department, Vall D’Hebron University Hospital (I.B.), and Institut Català D’Oncologia, Oncobell Program (IDIBELL), L’Hospitalet de Llobregat (M.G.-M.), Barcelona, and START Madrid-FJD, Hospital Fundación Jiménez Díaz, Madrid (V.M.) — all in Spain; Sarah Cannon Research Institute, Nashville (M.L.J.); and the Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta (T.K.O.). Address reprint requests to Dr. Migden at the Departments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, 1400 Pressler St. #1452, Houston, TX 73030, or at mrmigden@mdanderson.org.

 

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