Ipilimumab 改善转移性黑色素瘤患者的生存。
Improved survival with ipilimumab in patients with metastatic melanoma.
机构信息
Dana-Farber Cancer Institute, Boston, MA 02115, USA.
出版信息
N Engl J Med. 2010 Aug 19;363(8):711-23. doi: 10.1056/NEJMoa1003466. Epub 2010 Jun 5.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.)
背景
转移性黑色素瘤患者的总生存改善一直是一个难以实现的目标。在这项 3 期研究中，与单独使用 gp100 肽疫苗相比，阻断细胞毒性 T 淋巴细胞相关抗原 4 以增强抗肿瘤 T 细胞反应的伊匹单抗联合或不联合 gp100 用于治疗先前治疗过的转移性黑色素瘤患者。
方法
共有 676 名 HLA-A*0201 阳性的不可切除 III 期或 IV 期黑色素瘤患者，其疾病在转移性疾病治疗过程中进展，按 3:1:1 的比例随机分配接受伊匹单抗联合 gp100（403 例）、伊匹单抗单药（137 例）或 gp100 单药（136 例）治疗。伊匹单抗剂量为 3mg/kg，每 3 周使用一次，最多进行 4 次治疗（诱导）。符合条件的患者可接受再诱导治疗。主要终点是总生存。
结果
接受伊匹单抗联合 gp100 治疗的患者中位总生存时间为 10.0 个月，而接受 gp100 单药治疗的患者为 6.4 个月（死亡风险比，0.68；P<0.001）。伊匹单抗单药治疗的中位总生存时间为 10.1 个月（与 gp100 单药相比，死亡风险比为 0.66；P=0.003）。伊匹单抗组之间的总生存无差异（伊匹单抗联合 gp100 组的风险比为 1.04；P=0.76）。接受伊匹单抗治疗的患者中有 10%至 15%发生 3 级或 4 级免疫相关不良事件，而单独接受 gp100 治疗的患者中有 3%发生。有 14 例与研究药物相关的死亡（2.1%），其中 7 例与免疫相关不良事件相关。
结论
与单独使用 gp100 肽疫苗相比，伊匹单抗联合或不联合 gp100 可改善先前治疗的转移性黑色素瘤患者的总生存。不良事件可能严重、持久或两者兼而有之，但大多数可通过适当治疗逆转。（由 Medarex 和 Bristol-Myers Squibb 资助；ClinicalTrials.gov 编号，NCT00094653。）
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