Efficacy and safety of anti-PD-1 and anti-PD-1 combined with anti-CTLA-4 immunotherapy to advanced melanoma: A systematic review and meta-analysis of randomized controlled trials.
Efficacy and safety of anti-PD-1 and anti-PD-1 combined with anti-CTLA-4 immunotherapy to advanced melanoma: A systematic review and meta-analysis of randomized controlled trials.
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DOI：
10.1097/md.0000000000007325
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发表时间：
2017-06
期刊：
影响因子：
1.6
通讯作者：
Zhu B
中科院分区：
文献类型：
--
作者：
Hao C;Tian J;Liu H;Li F;Niu H;Zhu B
抗PD-1单克隆抗体nivolumab和pembrolizumab以及抗CTLA-4抗体ipilimumab正在临床试验中治疗黑素瘤。在这里，我们进行了荟萃分析，以评估他们对晚期黑色素瘤的疗效和毒性。纳入来自6项治疗转移性黑色素瘤的随机对照试验的11篇报告，分为3个亚组，nivolumab/pembrolizumab vs化疗，nivolumab vs ipilimumab，nivolumab + ipilimumab vs ipilimumab，并对每个亚组进行荟萃分析。结果指标为客观缓解率（ORR）、中位无进展生存期（PFS）、1年总生存率（OS）和3 - 4级不良事件估计的毒性。对于nivolumab/pembrolizumab vs化疗、nivolumab vs ipilimumab和nivolumab + ipilimumab vs ipilimumab，ORR的合并风险比（RR）分别为3.43（95% CI：2.57-4.58）、2.51（95% CI：2.03-3.09）和3.28（95% CI：2.58-4.17）。PFS的合并HR分别为0.42（95% CI：0.36-0.49）、0.58（95% CI：0.50-0.66）和0.41（95% CI：0.30-0.52）。纳武单抗与伊匹单抗以及纳武单抗+伊匹单抗与伊匹单抗的1年OS合并RR分别为1.37（95% CI：1.08-1.74）和1.54（95% CI：0.90-2.63）。这些结果表明，与对照组相比，抗PD-1单药治疗和nivolumab加ipilimumab治疗具有ORR和PFS获益。与伊匹单抗治疗相比，抗PD-1治疗增加了患者的1年OS。但nivolumab + ipilimumab治疗组与ipilimumab治疗组之间的1年OS无显著差异。毒性分析显示，与化疗和易普利姆玛组相比，抗PD-1治疗组发生不良事件的风险更低。与ipilimumab单独使用相比，nivolumab与ipilimumab联合使用增加了高级别不良事件的风险，但不良事件通常是可控的。抗PD-1单药治疗和nivolumab加ipilimumab治疗改善了晚期黑色素瘤患者的ORR并延长了PFS，并且不良事件通常是可管理的。该疗法确实是治疗晚期黑色素瘤的一种有前途的方法。
Anti-PD-1 monoclonal antibodies, nivolumab and pembrolizumab, and anti-CTLA-4 antibody ipilimumab are being in clinic trials to treat melanoma. Here, we performed a meta-analysis to evaluate the efficacy and toxicity of them against advanced melanoma. Eleven reports from 6 randomized control trials on treating metastatic melanoma, which were divided into 3 subgroups, nivolumab/pembrolizumab versus chemotherapy, nivolumab versus ipilimumab, and nivolumab-plus-ipilimumab versus ipilimumab, were included and the meta-analysis was performed for each subgroup. The outcome measures were objective response rates (ORR), median progression free survival (PFS), 1-year overall survival rates (OS), and toxicity estimated by grade 3 to 4 adverse events. For nivolumab/pembrolizumab versus chemotherapy, nivolumab versus ipilimumab, and nivolumab-plus-ipilimumab versus ipilimumab, the pooled risk ratios (RR) of the ORR were 3.43 (95% CI: 2.57–4.58), 2.51 (95% CI: 2.03–3.09), and 3.28 (95% CI: 2.58–4.17), respectively. The pooled HR of PFS were 0.42 (95% CI: 0.36–0.49), 0.58 (95% CI: 0.50–0.66), and 0.41 (95% CI: 0.30–0.52), respectively. The pooled RR of 1-year OS was 1.37 (95% CI: 1.08–1.74) and 1.54 (95% CI: 0.90–2.63) for nivolumab versus ipilimumab and nivolumab-plus-ipilimumab versus ipilimumab. These results suggested that anti-PD-1 monotherapy and nivolumab-plus-ipilimumab therapy had ORR and PFS benefit compared with the control group. Anti-PD-1 treatment increased 1-year OS for patients compared with ipililumab treatment. But there is no significantly difference on 1-year OS between the nivolumab-plus-ipilimumab treatment and the ipilimumab treatment group. The toxicity analysis showed that there is less risk of adverse events in the anti-PD-1 treatment group compared with the chemotherapy and ipilimumab group. Combining nivolumab with ipilimumab increased the risk for high-grade adverse events compared with ipilimumab alone but the adverse events were generally manageable. Anti-PD-1 monotherapy and nivolumab-plus-ipilimumab therapy improved ORR and prolonged PFS of patients with advanced melanoma and the adverse events are generally manageable. The therapy is indeed a promising approach for treatment of advanced melanoma.