gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma.
gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma.
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DOI：
10.1056/nejmoa1012863
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发表时间：
2011-06-02
期刊：
影响因子：
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通讯作者：
Hwu P
中科院分区：
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作者：
Schwartzentruber DJ;Lawson DH;Richards JM;Conry RM;Miller DM;Treisman J;Gailani F;Riley L;Conlon K;Pockaj B;Kendra KL;White RL;Gonzalez R;Kuzel TM;Curti B;Leming PD;Whitman ED;Balkissoon J;Reintgen DS;Kaufman H;Marincola FM;Merino MJ;Rosenberg SA;Choyke P;Vena D;Hwu P
使用疫苗刺激针对癌症的免疫反应仍然是一个挑战。我们假设将黑色素瘤疫苗与白细胞介素 2（一种免疫激活剂）相结合可以改善结果。在之前的一项 2 期研究中，接受高剂量 IL-2 联合 gp100:209–217(210M) 肽疫苗的转移性黑色素瘤患者的缓解率高于单独接受 IL-2 治疗的患者的预期缓解率。我们进行了一项随机 3 期试验，涉及 21 个中心的 185 名患者。资格标准包括 IV 期或局部晚期 III 期皮肤黑色素瘤、HLA⋆A0201表达、不存在脑转移以及适合高剂量白细胞介素 2 治疗。患者被随机分配接受单独的白细胞介素2（每剂每公斤体重720,000 IU）或gp100：209-217（210M）加不完全弗氏佐剂（Montanide ISA-51），每个周期一次，然后接受白细胞介素2。主要终点是临床反应。次要终点包括毒性作用和无进展生存期。治疗组在基线特征方面非常平衡，并且每个周期接受相似量的白细胞介素-2。毒性作用与白细胞介素 2 治疗的预期一致。与仅使用白介素 2 组相比，疫苗联合白细胞介素 2 组在集中验证的总体临床反应方面有显着改善（16% 对比 6%，P = 0.03），并且无进展生存期更长（2.2 个月；95% 置信区间 [CI]，1.7 至 3.9 对比 1.6 个月；95% CI，1.5 至 1.8；P = 0.008）。疫苗联合白细胞介素 2 组的中位总生存期也比仅白细胞介素 2 组长（17.8 个月；95% CI，11.9 至 25.8 个月 vs. 11.1 个月；95% CI，8.7 至 16.3；P = 0.06）。在晚期黑色素瘤患者中，与单独使用白细胞介素 2 相比，疫苗联合白细胞介素 2 治疗的缓解率更高，无进展生存期更长。 （由国家癌症研究所和其他机构资助；ClinicalTrials.gov 编号，NCT00019682。）
Stimulating an immune response against cancer with the use of vaccines remains a challenge. We hypothesized that combining a melanoma vaccine with interleukin-2, an immune activating agent, could improve outcomes. In a previous phase 2 study, patients with metastatic melanoma receiving high-dose interleukin-2 plus the gp100:209–217(210M) peptide vaccine had a higher rate of response than the rate that is expected among patients who are treated with interleukin-2 alone. We conducted a randomized, phase 3 trial involving 185 patients at 21 centers. Eligibility criteria included stage IV or locally advanced stage III cutaneous melanoma, expression of HLA⋆A0201, an absence of brain metastases, and suitability for high-dose interleukin-2 therapy. Patients were randomly assigned to receive interleukin-2 alone (720,000 IU per kilogram of body weight per dose) or gp100:209–217(210M) plus incomplete Freund’s adjuvant (Montanide ISA-51) once per cycle, followed by interleukin-2. The primary end point was clinical response. Secondary end points included toxic effects and progression-free survival. The treatment groups were well balanced with respect to baseline characteristics and received a similar amount of interleukin-2 per cycle. The toxic effects were consistent with those expected with interleukin-2 therapy. The vaccine–interleukin-2 group, as compared with the interleukin-2–only group, had a significant improvement in centrally verified overall clinical response (16% vs. 6%, P = 0.03), as well as longer progression-free survival (2.2 months; 95% confidence interval [CI], 1.7 to 3.9 vs. 1.6 months; 95% CI, 1.5 to 1.8; P = 0.008). The median overall survival was also longer in the vaccine–interleukin-2 group than in the interleukin-2–only group (17.8 months; 95% CI, 11.9 to 25.8 vs. 11.1 months; 95% CI, 8.7 to 16.3; P = 0.06). In patients with advanced melanoma, the response rate was higher and progression-free survival longer with vaccine and interleukin-2 than with interleukin-2 alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00019682.)