转移性葡萄膜黑色素瘤患者使用替本福司他治疗的 3 年总生存率。
Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma.
机构信息
From the University Hospital Heidelberg, Heidelberg (J.C.H.), the Department of Dermatology and Allergy, University Hospital, Ludwig Maximilian University of Munich, Munich (M.S.), and the Department of Dermatology, Venereology, and Allergology (M.S.) and the Department of Hematology, Oncology, and Tumor Immunology and the Comprehensive Cancer Center (S.O.), Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and the Department of Hematology, Oncology, and Tumor Immunology and the Comprehensive Cancer Center, Berlin Institute of Health (S.O.), Berlin - all in Germany; Institut Curie, Paris (S.P.-N.), and Centre Antoine Lacassagne, Nice (L.G.) - both in France; Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (P.R.); Institut Roi Albert II Cliniques Universitaires St-Luc, Université Catholique de Louvain, Brussels (J.-F.B.); Princess Margaret Cancer Centre, the Department of Medical Oncology and Hematology, and the Department of Immunology, University of Toronto, Toronto (M.O.B.); Massachusetts General Hospital and Dana-Farber Cancer Institute - both in Boston (R.J.S.); University of Zürich Hospital, Zürich, Switzerland (R.D.); University of Pittsburgh Medical Center, Pittsburgh (J.M.K.), Sidney Kimmel Cancer Center, Jefferson University, Philadelphia (M.O.), and Immunocore, Conshohocken (C.P.) - all in Pennsylvania; the Clatterbridge Cancer Centre NHS Foundation Trust, Wirral (J.J.S.), University of Liverpool, Liverpool (J.J.S.), Immunocore, Abingdon-on-Thames (L.C.), and Mount Vernon Cancer Centre, Northwood and UCLH, London (P.N.) - all in the United Kingdom; Kinghorn Cancer Centre, Saint Vincent's Hospital, Darlinghurst, NSW, Australia (A.M.J.); Providence Portland Medical Center, Portland, OR (B. Curti); Institut Català d'Oncologia and the Cancer Immunotherapy Group, OncoBell, Institut d'Investigació Biomèdica de Bellvitge, Barcelona, and Centro de Investigación Biomédica en Red de Cáncer, Madrid - all in Spain (J.M.P.); Duke University, Durham, NC (A.K.S.S.); Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York (A.N.S.), and Northwell Health Cancer Institute, New Hyde Park (R.D.C.) - all in New York; N.N. Blokhin National Medical Research Center of Oncology, Moscow (L.D.); University of Iowa Hospitals and Clinics, Iowa City (M.M.); Jonsson Comprehensive Cancer Center, University of California (B. Chmielowski), and the Angeles Clinic and Research Institute, Cedars-Sinai Affiliate (O.H.), Los Angeles, and California Pacific Medical Center, San Francisco (K.B.K.); and Immunocore, Rockville, MD (K.R., C.H.).
出版信息
N Engl J Med. 2023 Dec 14;389(24):2256-2266. doi: 10.1056/NEJMoa2304753. Epub 2023 Oct 21.
BACKGROUND
Tebentafusp, a T-cell receptor-bispecific molecule that targets glycoprotein 100 and CD3, is approved for adult patients who are positive for HLA-A*02:01 and have unresectable or metastatic uveal melanoma. The primary analysis in the present phase 3 trial supported a long-term survival benefit associated with the drug.
METHODS
We report the 3-year efficacy and safety results from our open-label, phase 3 trial in which HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma were randomly assigned in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with pembrolizumab, ipilimumab, or dacarbazine (control group), with randomization stratified according to the lactate dehydrogenase level. The primary end point was overall survival.
RESULTS
At a minimum follow-up of 36 months, median overall survival was 21.6 months in the tebentafusp group and 16.9 months in the control group (hazard ratio for death, 0.68; 95% confidence interval, 0.54 to 0.87). The estimated percentage of patients surviving at 3 years was 27% in the tebentafusp group and 18% in the control group. The most common treatment-related adverse events of any grade in the tebentafusp group were rash (83%), pyrexia (76%), pruritus (70%), and hypotension (38%). Most tebentafusp-related adverse events occurred early during treatment, and no new adverse events were observed with long-term administration. The percentage of patients who discontinued treatment because of adverse events continued to be low in both treatment groups (2% in the tebentafusp group and 5% in the control group). No treatment-related deaths occurred.
CONCLUSIONS
This 3-year analysis supported a continued long-term benefit of tebentafusp for overall survival among adult HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma. (Funded by Immunocore; IMCgp100-202 ClinicalTrials.gov number, NCT03070392; EudraCT number, 2015-003153-18.).
背景
Tebentafusp 是一种 T 细胞受体双特异性分子，靶向糖蛋白 100 和 CD3，已获批准用于 HLA-A*02:01 阳性、不可切除或转移性葡萄膜黑色素瘤的成年患者。本 3 期临床试验的主要分析支持该药物与长期生存获益相关。
方法
我们报告了一项开放标签、3 期临床试验的 3 年疗效和安全性结果，该试验入组了未经治疗的转移性葡萄膜黑色素瘤的 HLA-A*02:01 阳性患者，这些患者以 2:1 的比例随机分配至接受 Tebentafusp（Tebentafusp 组）或研究者选择的治疗方案（包括 pembrolizumab、ipilimumab 或 dacarbazine），随机分组时根据乳酸脱氢酶水平进行分层。主要终点为总生存期。
结果
在至少 36 个月的随访中，Tebentafusp 组的中位总生存期为 21.6 个月，对照组为 16.9 个月（死亡风险比，0.68；95%置信区间，0.54 至 0.87）。Tebentafusp 组 3 年时的估计生存率为 27%，对照组为 18%。Tebentafusp 组任何级别最常见的治疗相关不良事件是皮疹（83%）、发热（76%）、瘙痒（70%）和低血压（38%）。大多数 Tebentafusp 相关不良事件发生在治疗早期，长期用药未观察到新的不良事件。两组因不良事件而停止治疗的患者比例继续保持较低水平（Tebentafusp 组为 2%，对照组为 5%）。未发生与治疗相关的死亡。
结论
这项 3 年分析支持 Tebentafusp 继续为未经治疗的 HLA-A*02:01 阳性转移性葡萄膜黑色素瘤成年患者带来总体生存获益。（由 Immunocore 资助；IMCgp100-202 临床试验.gov 编号，NCT03070392；EudraCT 编号，2015-003153-18。）
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