贝尔祖提凡与埃弗罗利斯对抗晚期细胞癌
Toni K Choueiri1, Thomas Powles1, Katriina Peltola1
1From Dana-Farber Cancer Institute, Boston (T.K.C.); Barts Cancer Centre, Queen Mary University of London BRC, Royal Free NHS Trust, London (T.P.), and Beatson West of Scotland Cancer Centre and the University of Glasgow, Glasgow (B.V.) - all in the United Kingdom; HUS Helsinki University Hospital, Comprehensive Cancer Center, Helsinki (K.P.); University Hospital 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid (G.V.), and Medical Oncology, Vall d´Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus (C.S.), and Institute Catalan of Oncology-ICO-IDIBELL University of Barcelona (X.G.-M.), Barcelona - all in Spain; Bradford Hill Clinical Research Center, Santiago, Chile (M.B.); Fox Chase Cancer Center, Philadelphia (P.G.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (R.I.), Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (E.V.), the University of Bari "A. Moro" and Azienda Ospedaliera Policlinico di Bari, Bari (C.P.), and Fondazione Salvatore Maugeri clinica del lavoro, Pavia (E.B.) - all in Italy; the University of Colorado Cancer Center, Aurora (E.T.L.); Istanbul Medeniyet University, Prof. Dr. Suleyman Yalcin City Hospital, Istanbul, Turkey (M.G.); the University of Chicago Medical Center, Chicago (W.M.S.); BC Cancer-Vancouver Center, Vancouver, BC, Canada (C.K.); the Department of Oncology, Palacký University and University Hospital, Olomouc (B.M.), and the Department of Comprehensive Cancer Care and Faculty of Medicine, Masaryk Memorial Cancer Institute and Masaryk University, Brno (A.P.) - both in the Czech Republic; University Hospital Bordeaux-Hôpital Saint-André, Bordeaux (M.G.-G.), and Département de Médecine Oncologique, Gustave Roussy, Université Paris Saclay, Villejuif (L.A.) - both in France; Charité Universitaetsmedizin Berlin, Department of Urology, Berlin (M.D.S.); the Department of Urology, Medical University of Vienna, Vienna (M.D.S.); BP-A Beneficencia Portuguesa de São Paulo, Sao Paulo (F.A.S.); Samsung Medical Center, Sungkyunkwan University School of Medicine (S.H.P.), and Asan Medical Center, University of Ulsan College of Medicine (J.L.L.) - both in Seoul, South Korea; Central Clinical Hospital with Polyclinic, Moscow (D.A.N.); Sociedad de Oncología y Hematología del Cesar, Valledupar, Colombia (R.M.K.); Keio University Hospital, Tokyo (M.O.); Merck, Rahway, NJ (L.H., A.W., R.F.P., D.V.); and Vanderbilt Ingram Cancer Center, Nashville (B.R.).
贝尔祖提凡显著改善了先前使用其他疗法治疗的晚期清细胞细胞癌患者的无进展生存率和客观应答率. 这种低氧诱导的2α因子抑制剂与everolimus相比显示出有利的益处风险概况.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 清细胞细胞癌 (ccRCC) 是一个重要的瘤挑战,特别是在晚期.
- 低氧诱导因子2α (HIF-2α) 是ccRCC发病的一个关键驱动因素.
- 新型HIF-2α抑制剂Belzutifan已经显示出早期临床前景.
研究的目的:
- 为了评估贝尔祖提凡的疗效和安全性,与埃弗罗利斯相比,在晚期ccRCC患者中.
- 评估无进展生存率 (PFS),总生存率 (OS) 和客观反应率 (ORR).
- 调查贝尔祖提凡在患者中所扮演的角色,这些患者在先前的免疫检查点和抗血管生成疗法中不耐药.
主要方法:
- 一个第三阶段,多中心,开放标签,主动控制试验 (LITESPARK-005).
- 374名参与者接受了贝尔祖提凡 (每天120毫克),372人接受了常利 (每天10毫克).
- 双重主要终点:PFS和OS. 关键的次要终点:ORR.
主要成果:
- 贝尔祖提凡显著改善了PFS (中位数为5.6个月与5.6个月,P=0.002在18个月) 和ORR (21.9%与3.5%,P<0.001).
- 贝尔祖提芬的中位寿命为21.4个月,而埃弗罗利斯的平均寿命为18.1个月 (HR 0.88,P=0.20).
- 3级+不良事件的发生率相似 (61.8%与62.5%相比),由于贝尔祖提凡的副作用而导致的治疗中止率较低 (5.9%与14.7%相比).
结论:
- 在先进的ccRCC患者中,贝尔祖提凡比everolimus具有显著的治疗益处,这些患者接受了免疫检查点和抗血管原剂的预治疗.
- 该药物显示出优异的PFS和ORR,具有可管理的安全性.
- 贝尔祖蒂芬代表了这个患者群体的有价值的新治疗选择.
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