Checkpoint inhibitors for malignant melanoma: a systematic review and meta-analysis.
Checkpoint inhibitors for malignant melanoma: a systematic review and meta-analysis.
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DOI：
10.2147/ccid.s120877
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Saleh SN
中科院分区：
文献类型：
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作者：
Karlsson AK;Saleh SN
恶性黑色素瘤的发病率在持续增加，直到最近还缺乏有效的治疗方法。然而，自2011年以来，已有三种被称为检查点抑制剂的免疫治疗药物获得批准。这篇综述旨在确定这三种药物-ipilimumab、nivolumab和pembrolizumab-是否比对照干预(安慰剂、免疫治疗或化疗)在III或IV期不能切除的皮肤黑色素瘤患者中提供更好的疗效和耐受性。对四个主要医学和科学数据库的搜索产生了7553条记录，其中7条符合纳入标准，研究总人数为3628人。只有II期或III期的前瞻性随机对照试验针对不能切除的皮肤黑色素瘤患者，这些试验报告了生存(总体或无进展)、肿瘤反应或不良事件的数据。本研究共进行了三项荟萃分析。进展或死亡的危险比为0.54(95%可信区间：0.44-0.67)，最佳总应答率的优势比为4.48(95%可信区间：2.77-7.24)，均支持检查点抑制剂。然而，对照治疗与因不良反应或与治疗相关的不良事件而中断治疗的比率无显著差异(优势比=1.63[95%CI：0.55-4.88])。这项研究发现，无论是在存活率和肿瘤反应方面，检查点抑制剂都比对照干预更有效，但耐受性并不比对照组差。PD1疗法(nivolumab和pembrolizumab)似乎比CTLA4疗法(Ipilimumab)提供更好的疗效。然而，nivolumab和ipilimumab的组合是最有效的，但耐受性明显低于单一疗法。然而，缺乏已发表的临床数据确实限制了这项研究。特别是在两个领域需要进一步研究：1)确定检查点抑制剂的最佳使用，特别是在联合治疗方面；2)为预测性应答者确定可靠的生物标志物，并指导治疗分配。
Rates of malignant melanoma are continuing to increase, and until recently effective treatments were lacking. However, since 2011 three immunotherapeutic agents, known as checkpoint inhibitors, have been approved. This review aims to establish whether these three drugs – ipilimumab, nivolumab, and pembrolizumab – offer greater efficacy and tolerability compared to control interventions (placebo, immunotherapy, or chemotherapy) in patients with stage III or IV unresectable cutaneous melanoma. A search on four major medical and scientific databases yielded 7,553 records, of which seven met the inclusion criteria, with a total study population of 3,628. Only prospective Phase II or III randomized controlled trials on checkpoint inhibitors for patients with unresectable cutaneous melanoma that reported data on survival (overall or progression-free), tumor response, or adverse events were included. Three meta-analyses were carried out. The hazard ratio for progression or death was 0.54 (95% confidence interval [CI]: 0.44–0.67), and the odds ratio for best overall response rate was 4.48 (95% CI: 2.77–7.24), both in favor of checkpoint inhibitors. However, control treatments were associated with an insignificantly lower rate of discontinuation of treatment due to adverse effects or treatment-related adverse events (odds ratio =1.63 [95% CI: 0.55–4.88]). This study finds that checkpoint inhibitors are more effective than control interventions, both in terms of survival and tumor response, and yet no less tolerable. PD1 therapies (nivolumab and pembrolizumab) appear to offer greater efficacy than CTLA4 therapy (ipilimumab). The combination of nivolumab and ipilimumab was, however, the most effective, but significantly less tolerable than monotherapy. The lack of published clinical data does, however, limit this study. Further research is needed in two areas in particular: 1) to determine the optimal use of checkpoint inhibitors, specifically in terms of combination therapy, and 2) to identify reliable biomarkers to predictive responders and guide treatment assignment.