在III期黑色素瘤中,助剂达布拉费尼布加上特拉美替尼布的最终结果
Georgina V Long1, Axel Hauschild1, Mario Santinami1
1From the Melanoma Institute Australia, the University of Sydney, Royal North Shore Hospital, and Mater Hospital, Sydney (G.V.L.), Princess Alexandra Hospital, the Gallipoli Medical Research Foundation, and the University of Queensland, Woolloongabba (V.A.), and Alfred Hospital, Melbourne, VIC (A.H.) - all in Australia; the Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel (A.H.), and the German Cancer Consortium, National Center for Tumor Diseases, University Hospital Essen, Campus Essen, and the University Alliance Ruhr, Research Center One Health, University of Duisburg-Essen, Essen (D.S.) - all in Germany; Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan (M.S.), the Unit of Medical Oncology, Department of Oncology and Hematology, Papa Giovanni XXIII Cancer Center Hospital, Bergamo (B.M., M.M.), and Oncology 2, Veneto Institute of Oncology IOV-IRCCS, Padua (V.C.S.) - all in Italy; the Melanoma Program, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.); Oslo University Hospital and the Norwegian Radium Hospital, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux and Hôpital Saint-André, Bordeaux (C.D.), Gustave Roussy and Paris-Sud-Paris-Saclay University, Villejuif (C.R.), Université de Lille, INSERM Unité 1189, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; the Ella Lemelbaum Institute for Immuno Oncology and Melanoma, Sheba Medical Center, and the Sackler School of Medicine, Tel-Aviv University, Ramat Gan, Israel (J.S.); Northern Centre for Cancer Care, Freeman Hospital, and Newcastle University, Newcastle (R.P.), and the Royal Marsden National Health Services Foundation Trust, London (J.L.) - all in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (M.T.); Novartis Healthcare, Hyderabad, India (S.B.A., T.J.); and Novartis Pharma, Basel (P.B.), and the University Hospital Zürich Skin Cancer Center, Zurich (R.D.) - both in Switzerland.
助剂达布拉费尼布加上特拉美丁尼布在III期黑色素瘤患者中改善了无复发和远程转移的生存期. 虽然整体存活率显示了益处的趋势,但在这个长期试验中,它在统计学上没有显著意义.
科学领域:
- 在瘤学瘤学.
- 临床试验 临床试验
- 皮肤病学 皮肤病学
背景情况:
- 患有BRAF V600突变的III期黑色素瘤是一个重大的治疗挑战.
- 辅助疗法旨在减少手术切除后复发的风险.
- 之前的试验表明,达布拉费尼布加上特拉美替尼布有好处,需要长期生存数据.
研究的目的:
- 报告COMBI-AD试验的最终长期整体生存 (OS) 结果.
- 评估助剂达布拉费尼布加特拉美丁尼布与安慰剂在切除的III期黑色素瘤中的疗效.
- 评估黑色素瘤特异性存活率,无复发存活率 (RFS) 和无远程转移存活率 (DMFS).
主要方法:
- 一个随机,双盲,安慰剂对照试验,涉及870名患有切除的III期黑色素瘤和BRAF V600突变的患者.
- 患者接受了12个月的达布拉费尼布 (150毫克两次) 加上特拉美丁尼布 (2毫克四次) 或匹配的安慰剂.
- 最终分析包括OS,黑色素瘤特异性生存率,RFS和DMFS,随访时间中位数为8.33年.
主要成果:
- 与安慰剂相比,助剂达布拉费尼布加上特拉美替尼布显著改善了RFS (HR 0.52) 和DMFS (HR 0.56).
- 综合治疗的整体存活率呈现出良好的趋势 (HR 0.80,P=0.06),表明死亡风险降低了20%.
- 在BRAF V600E突变 (HR 0.75) 的小组中观察到显著的生存益处. 没有发现新的安全问题.
结论:
- 助剂达布拉费尼布加上特拉美丁尼布在改善RFS和DMFS治疗切除的III期黑色素瘤方面表现出持久的疗效.
- 组合疗法显示整体存活率的非显著但临床相关的改善.
- 长期数据支持在BRAF突变黑色素瘤,特别是V600E亚型中使用dabrafenib加上trametinib.


