纳武利尤单抗联合伊匹木单抗治疗晚期黑色素瘤的 5 年生存数据
Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma.
机构信息
From the Royal Marsden NHS Foundation Trust, London (J.L.), and the College of Medicine, Swansea University, Swansea (J.W.) - both in the United Kingdom; the Oncology Institute of Veneto IRCCS, Padua (V.C.-S.), the European Institute of Oncology, IRCCS, Milan (P.F.F.), Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples (P.A.A.), the Immunotherapy and Somatic Cell Therapy Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (M.G.), and the Center for Immuno-Oncology, Medical Oncology and Immunotherapy, University Hospital, Siena (M.M.) - all in Italy; the University of Colorado Cancer Center, Aurora (R.G.); Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille Hôpital Timone, Marseille (J.-J.G.), and Université de Paris, INSERM Unité 976, Assistance Publique-Hôpitaux de Paris Dermatology and Centres d'Investigation Clinique, Saint Louis Hospital, Paris (C.L.) - both in France; the Maria Sklodowska-Curie Institute-Oncology Center, Warsaw, Poland (P.R.); the University of Michigan, Ann Arbor (C.D.L.); Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas (C.L.C.); the Department of Dermatology, University of Essen, Essen, and the German Cancer Consortium, Heidelberg - both in Germany (D.S.); Universitäts Spital, Zurich, Switzerland (R.D.); Cross Cancer Institute, Edmonton, AB (M.S.), and the Princess Margaret Cancer Centre, Toronto (D.H.) - both in Canada; Tasman Oncology Research, Southport, QLD (A.H.), the Crown Princess Mary Cancer Centre, Melanoma Institute Australia, University of Sydney, Sydney, NSW (M.S.C., G.V.L.), and the Royal North Shore and Mater Hospitals (G.V.L.), Sydney, and the Peter MacCallum Cancer Centre, Melbourne, VIC (G.M.) - all in Australia; General University Hospital Gregorio Marañon and Centro de Investigación Biomédica en Red de Oncología, Madrid (I.M.-R.); the Netherlands Cancer Institute, Amsterdam (J.H.); the Leuven Cancer Institute, Department of General Medical Oncology, University Hospital Leuven, Leuven, Belgium (P.S.); University of California San Diego Health-La Jolla Moores Cancer Center, La Jolla (G.A.D.); the Department of Oncology, Odense University Hospital, Odense, Denmark (L.B.); Bristol-Myers Squibb, Princeton, NJ (J.I.R., A.B., A.M.); Dana-Farber Cancer Institute, Boston (F.S.H.); and the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (J.D.W.).
出版信息
N Engl J Med. 2019 Oct 17;381(16):1535-1546. doi: 10.1056/NEJMoa1910836. Epub 2019 Sep 28.
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. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).
背景
纳武单抗联合伊匹单抗或纳武单抗单药治疗与伊匹单抗单药治疗相比，可延长晚期黑色素瘤患者的无进展生存期和总生存期。现将该试验的 5 年结果报告如下。
方法
我们将未经治疗的晚期黑色素瘤患者随机分配至以下治疗组：纳武单抗（1mg/kg，每 3 周 1 次）联合伊匹单抗（3mg/kg，每 3 周 1 次）共 4 次，随后纳武单抗（3mg/kg，每 2 周 1 次）；纳武单抗（每 2 周 3mg/kg）联合伊匹单抗安慰剂；或伊匹单抗（每 3 周 3mg/kg 共 4 次）联合纳武单抗安慰剂。主要终点是纳武单抗联合伊匹单抗组和纳武单抗组的无进展生存期和总生存期，与伊匹单抗组进行比较。
结果
在至少 60 个月的随访中，纳武单抗联合伊匹单抗组的中位总生存期超过 60.0 个月（未达到中位生存期），纳武单抗组为 36.9 个月，而伊匹单抗组为 19.9 个月（纳武单抗联合伊匹单抗组与伊匹单抗组的死亡风险比为 0.52；纳武单抗组与伊匹单抗组的死亡风险比为 0.63）。纳武单抗联合伊匹单抗组的 5 年总生存率为 52%，纳武单抗组为 44%，而伊匹单抗组为 26%。纳武单抗联合伊匹单抗或纳武单抗单药治疗期间或治疗后未观察到健康相关生活质量的持续恶化。未发现新的晚期毒性作用。
结论
在晚期黑色素瘤患者中，与伊匹单抗单药治疗相比，接受纳武单抗联合伊匹单抗或纳武单抗单药治疗的患者中，有更高比例的患者持续长期生存至 5 年，且接受纳武单抗治疗方案的患者生活质量无明显下降。（由 Bristol-Myers Squibb 等人资助；CheckMate 067 临床试验.gov 编号，NCT01844505）。
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