新辅助药Nivolumab和Ipilimumab在可切割的III期黑色素瘤中使用
Christian U Blank1, Minke W Lucas1, Richard A Scolyer1
1From the Departments of Medical Oncology (C.U.B., M.W.L., L.L.H., J.M.L., S.M.P., J.B.A.G.H., K.A.T.N., J.V.T., S.W., A.M.-E., I.L.M.R.), Pathology (B.A.W.), Biometrics (M.L.-Y., A.T.A., L.G.G.-O.), Surgical Oncology (W.J.H., A.M.J.K., A.C.J.A.), Head and Neck Surgery (W.M.C.K., C.L.Z.), Radiology (B.A.S.), and Molecular Oncology and Immunology (J.B.A.G.H.), Netherlands Cancer Institute, and the Department of Medical Oncology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Cancer Center Amsterdam (A.J.M.E.), Amsterdam, the Departments of Medical Oncology (C.U.B., J.B.A.G.H., F.M.S., E.K.) and Otorhinolaryngology Head and Neck Surgery (C.L.Z.), Leiden University Medical Center, Leiden, the Departments of Medical Oncology (K.A.T.N., R.C.S., A.A.M.V.), Surgical Oncology (D.J.G., R.C.S.), and Radiology and Nuclear Medicine (A.A.M.V.), Erasmus Medical Center, Rotterdam, the Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht (S.B.V., K.P.M.S.), the Department of Medical Oncology, Medical Center Leeuwarden, Leeuwarden (R.R.), the Department of Medical Oncology, Zuyderland Medical Center, Sittard-Geleen (F.W.P.J.B.), the Department of Medical Oncology, Medisch Spectrum Twente, Enschede (D.P.), the Department of Medical Oncology, Maxima Medical Center, Veldhoven (G.V.), the Department of Medical Oncology, Maastricht University Medical Center, GROW School for Oncology and Developmental Biology, Maastricht (M.J.B.A.), the Department of Medical Oncology, Amphia Hospital, Breda (M.A.M.S.B.), the Department of Medical Oncology, Radboud University Medical Center, Nijmegen (M.J.B.-S.), the Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen (G.A.P.H.), and Isala Oncology Center, Isala Hospital, Zwolle (J.-W.B.G.) - all in the Netherlands; the Department of Hematology and Medical Oncology, University Clinic Regensburg, Regensburg, Germany (C.U.B.); Melanoma Institute Australia (R.A.S., A.M.M., R.P.M.S., N.G.M., M.G., S.N.L., A.S., T.E.P., K.F.S., R.V.R., S.C., J.S., M.A.R., A.C.J.A., M.S.C., G.V.L.), the Faculty of Medicine and Health (R.A.S., A.M.M., R.P.M.S., N.G.M., S.N.L., A.S., T.E.P., K.F.S., S.C., J.S., M.A.R., A.C.J.A., G.V.L.), and Charles Perkins Centre (R.A.S., G.V.L.), University of Sydney, the Departments of Tissue Pathology and Diagnostic Oncology (R.A.S., R.V.R.) and Melanoma and Surgical Oncology (R.P.M.S., T.E.P., K.F.S., S.C., J.S., M.A.R., A.C.J.A.), Royal Prince Alfred Hospital, NSW Health Pathology (R.A.S., R.V.R.), the Departments of Medical Oncology (A.M.M., G.V.L.) and Breast and Melanoma Surgery (A.S.), Royal North Shore and Mater Hospitals, and the Department of Radiology, Mater Hospital (R.K.), Sydney, Royal Prince Alfred Hospital, Institute of Academic Surgery, Camperdown, NSW (A.C.J.A.), the Division of Cancer Surgery, Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC (D.E.G.), the Department of Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, VIC (L.S., S.S.), Lake Macquarie Oncology, Lake Macquarie Private Hospital, the Department of Medical Oncology, Calvary Mater Hospital, and the Department of Medicine, School of Medicine and Public Health, University of Newcastle, Newcastle, NSW (A.W.), the Department of Medical Oncology, Princess Alexandra Hospital, University of Queensland, Brisbane (V.A.), the Department of Medical Oncology, Fiona Stanley Hospital, Perth, WA (M.K.), the Department of Medical Oncology, Alfred Health, Melbourne, and the Department of Medicine, School of Translational Medicine, Monash University, Melbourne, VIC (M.C.A.), and the Department of Medical Oncology, Westmead Hospital and Blacktown, Sydney (M.S.C.) - all in Australia; the Melanoma Clinic, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland (J.B.A.G.H.); the Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (J.P., P.R.); the Department of Medical Oncology, Centre Léon Bérard, Lyon (M.A.-A.), Université Paris Cité, Assistance Publique-Hôpitaux de Paris (AP-HP) Dermato-Oncology and Clinical Investigation Center, Cancer Institute AP-HP, Nord Paris Cité, INSERM Unité 976, Saint Louis Hospital, Paris (C.L.), and the Department of Medical Oncology, Gustave Roussy and Paris-Saclay University, Villejuif (C.R.) - all in France; the Department of Surgical Oncology, Angeles Clinic and Research Institute, Los Angeles (M.B.F.); and the Melanoma Cancer Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy (P.A.A.).
与辅助药尼沃卢马布相比,新辅助药伊皮利穆马布加尼沃卢马布在III期黑色素瘤患者中显著改善了无事件生存率. 这种组合疗法为切除性黑色素瘤提供了一种有希望的新方法.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 黑色素瘤研究 黑色素瘤研究
背景情况:
- 以前的1-2期试验表明,新辅助免疫疗法在可切除,宏观的III期黑色素瘤中比辅助免疫疗法更有效.
- 第三阶段黑色素瘤是一个重大挑战,需要探索最佳治疗策略以改善患者的治疗结果.
研究的目的:
- 为了比较新辅助药伊皮利穆马布加尼沃卢马布后进行手术的疗效,与在可切除的,宏观的III期黑色素瘤患者中接受辅助药尼沃卢马布后进行手术的疗效.
- 在这个第三阶段试验中,评估无事件生存率作为主要终点.
主要方法:
- 一项3期随机试验,涉及423名可切除,宏观性III期黑色素瘤患者.
- 患者在手术前被分配给两轮新辅助性伊皮利穆马布加尼沃卢马布治疗,或手术后得到辅助性尼沃卢马布治疗.
- 响应驱动辅助疗法被给予新辅助组患者,部分反应或无反应.
主要成果:
- 与辅助剂组 (57.2%) 相比,新辅助剂组的12个月无事件生存率 (83.7%) 显着更高.
- 在新辅助手臂的59.0%患者中观察到主要的病理反应,与改善的无复发生存率相关.
- 3级或更高的与治疗相关的不良事件在新辅助剂组 (29.7%) 比辅助剂组 (14.7%) 更频繁.
结论:
- 新辅助药伊皮利穆马布加尼沃卢马布,然后进行手术和响应驱动的辅助疗法,显著提高可切除,宏观性III期黑色素瘤的无事件生存率.
- 这些发现支持新辅助免疫疗法作为优越的治疗策略,与辅助疗法相比,在这个患者群体中.
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