Improved survival with ipilimumab in patients with metastatic melanoma.
Improved survival with ipilimumab in patients with metastatic melanoma.
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DOI：
10.1056/nejmoa1003466
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发表时间：
2010-08-19
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影响因子：
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通讯作者：
Urba WJ
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作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
改善转移性黑色素瘤患者的总体生存率一直是一个难以实现的目标。在这项3期研究中，在既往接受过治疗的转移性黑色素瘤患者中，将ipilimumab（可阻断细胞毒性T淋巴细胞相关抗原4，以增强抗肿瘤T细胞应答）与糖蛋白100（gp 100）肽疫苗联合或不联合给药与单独使用gp 100进行了比较。共有676例HLA-A β 0201阳性的不可切除的III期或IV期黑色素瘤患者，在接受转移性疾病治疗时疾病进展，以3：1：1的比例随机分配接受ipilimumab + gp 100（403例患者），ipilimumab单药（137例）或gp 100单药（136例）。伊匹单抗的剂量为3 mg/kg体重，每3周一次（有或无gp 100）给药，最多给药4次（诱导）。符合条件的患者可以接受再诱导治疗。主要终点是总生存期。接受ipilimumab联合gp 100治疗的患者的中位总生存期为10.0个月，而仅接受gp 100治疗的患者为6.4个月（死亡风险比为0.68; P<0.001）。单用ipilimumab的中位总生存期为10.1个月（与单用gp 100相比，死亡风险比为0.66; P = 0.003）。在易普利姆玛组之间没有检测到总生存率的差异（易普利姆玛加gp 100的风险比，1.04; P = 0.76）。3级或4级免疫相关不良事件发生在10%至15%的ipilimumab治疗患者和3%的gp 100单独治疗患者中。有14例死亡与研究药物相关（2.1%），7例与免疫相关不良事件相关。与单独使用gp 100相比，伊匹单抗联合或不联合gp 100肽疫苗可改善既往接受过治疗的转移性黑色素瘤患者的总体生存率。不良事件可能是严重的，长期的，或两者兼而有之，但大多数是可逆的适当治疗。（由Medarex和Bristol-Myers Squibb资助; ClinicalTrials.gov编号，NCT 00094653。
An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab — which blocks cytotoxic T-lymphocyte–associated antigen 4 to potentiate an antitumor T-cell response — administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. A total of 676 HLA-A⋆0201–positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P = 0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P = 0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)