聯合療法可提高晚期黑色素瘤5年生存率
作者：
小柯機器人發布時間：2019/9/29 16:04:31
英國倫敦皇家馬斯登NHS基金會James Larkin等研究人員，探究了Nivolumab和依普利單抗聯合治療晚期黑色素瘤的5年生存率。2019年9月28日，《新英格蘭醫學雜誌》在線發表了這項成果。
在一項涉及晚期黑色素瘤患者的試驗中，與單獨使用依普利單抗相比，Nivolumab聯合依普利單抗或Nivolumab單藥治療均顯著延長了患者的無進展和總生存期。該研究擴展了5年的試驗結果。
研究人員隨機分配先前未經治療的晚期黑色素瘤患者接受以下治療方案之一：Nivolumab（每公斤體重1毫克）+依普利單抗（每公斤3毫克）每3周一次，共4次，之後Nivolumab（每公斤3毫克）每2周一次；Nivolumab（每公斤3毫克）+安慰劑，每2周一次；或依普利單抗（每公斤3毫克）+安慰劑，每3周一次，共4次。
在至少60個月的隨訪中，依普利單抗組的中位總生存期為19.9個月，Nivolumab+依普利單抗組為60個月，死亡風險比為0.52；Nivolumab組為36.9個月，死亡風險比為0.63。Nivolumab+依普利單抗組的5年總生存率為52%，Nivolumab組為44%，而依普利單抗組為26%。在使用Nivolumab+依普利單抗或單獨Nivolumab治療期間或之後，均未觀察到與健康相關的生活質量持續惡化，亦未發現新的晚期毒性作用。
總之，接受Nivolumab+依普利單抗或Nivolumab單藥治療的晚期黑色素瘤患者，5年持續長期總生存率顯著高於單獨依普利單抗治療的患者，且生活質量未明顯下降。
附：英文原文
Title:Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma
Author:James Larkin, F.R.C.P., Ph.D., Vanna Chiarion-Sileni, M.D., Rene Gonzalez, M.D., Jean-Jacques Grob, M.D., Piotr Rutkowski, M.D., Ph.D., Christopher D. Lao, M.D., C. Lance Cowey, M.D., M.P.H., Dirk Schadendorf, M.D., John Wagstaff, M.D., Reinhard Dummer, M.D., Pier F. Ferrucci, M.D., Michael Smylie, M.D., David Hogg, M.D., Andrew Hill, M.D., Ivan Márquez-Rodas, M.D., Ph.D., John Haanen, M.D., Massimo Guidoboni, M.D., Michele Maio, M.D., Patrick Schöffski, M.D., Ph.D., Matteo S. Carlino, M.D., Céleste Lebbé, M.D., Ph.D., Grant McArthur, F.R.A.C.P., Ph.D., Paolo A. Ascierto, M.D., Gregory A. Daniels, M.D., Georgina V. Long, M.D., Lars Bastholt, M.D., Jasmine I. Rizzo, M.D., M.P.H., Agnes Balogh, M.Sc., Andriy Moshyk, M.D., F. Stephen Hodi, M.D., and Jedd D. Wolchok, M.D., Ph.D.
Issue&Volume:2019-09-28
Abstract:
BACKGROUND
Nivolumab plus ipilimumab or nivolumab alone resulted in longer progression-free and overall survival than ipilimumab alone in a trial involving patients with advanced melanoma. We now report 5-year outcomes in the trial.
METHODS
We randomly assigned patients with previously untreated advanced melanoma to receive one of the following regimens: nivolumab (at a dose of 1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram every 2 weeks); nivolumab (3 mg per kilogram every 2 weeks) plus ipilimumab-matched placebo; or ipilimumab (3 mg per kilogram every 3 weeks for four doses) plus nivolumab-matched placebo. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group, as compared with the ipilimumab group.
RESULTS
At a minimum follow-up of 60 months, the median overall survival was more than 60.0 months (median not reached) in the nivolumab-plus-ipilimumab group and 36.9 months in the nivolumab group, as compared with 19.9 months in the ipilimumab group (hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab, 0.52; hazard ratio for death with nivolumab vs. ipilimumab, 0.63). Overall survival at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, as compared with 26% in the ipilimumab group. No sustained deterioration of health-related quality of life was observed during or after treatment with nivolumab plus ipilimumab or with nivolumab alone. No new late toxic effects were noted.
CONCLUSIONS
Among patients with advanced melanoma, sustained long-term overall survival at 5 years was observed in a greater percentage of patients who received nivolumab plus ipilimumab or nivolumab alone than in those who received ipilimumab alone, with no apparent loss of quality of life in the patients who received regimens containing nivolumab.
DOI:10.1056/NEJMoa1910836