免疫检查点抑制剂联合治疗晚期肾细胞癌的疗效和毒性：系统评价和网络荟萃分析。
Efficacy and toxicity of immune checkpoint inhibitors combination therapy for advanced renal cell carcinoma: a systematic review and network meta-analysis.
机构信息
Department of Urology, Tianjin Medical University General Hospital, Tianjin, China.
出版信息
Front Immunol. 2024 Feb 8;15:1255577. doi: 10.3389/fimmu.2024.1255577. eCollection 2024.
BACKGROUND
Although immune checkpoint inhibitors (ICIs) show a significant overall survival advantage over standard advanced renal cell carcinoma (aRCC) therapies, tumor response to these agents remains poor. Some studies have shown that combination therapy including an ICI appears to be the best treatment; however, the overall benefit in terms of efficacy and toxicity still needs to be assessed. Thus, we performed a network meta-analysis to evaluate the differences in the efficacy of several combinations that include an ICI to provide a basis for clinical treatment selection.
METHODS
We conducted a thorough search of PubMed, EMBASE, and the Cochrane Library for articles from January 2010 to June 2023. R 4.4.2 and STATA 16.0 were used to analyze data; hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CI) were used to assess the results.
RESULTS
An indirect comparison showed that nivolumab plus cabozantinib and pembrolizumab plus lenvatinib were the most effective treatments for progression-free survival (PFS), with no significant differences between the two interventions (HR, 1.31; 95% CI, 0.96-1.78; P=0.08); rank probability showed that pembrolizumab plus lenvatinib had a 57.1% chance of being the preferred treatment. In the absence of indirect comparisons between pembrolizumab plus axitinib, nivolumab plus ipilimumab, avelumab plus axitinib, nivolumab plus cabozantinib, and pembrolizumab plus lenvatinib, pembrolizumab plus axitinib (40.2%) was the best treatment option for overall survival (OS). Compared to pembrolizumab plus lenvatinib, nivolumab plus ipilimumab (OR, 0.07; 95% CI, 0.01-0.65; P=0.02) and pembrolizumab plus axitinib (OR, 0.05; 95% CI, 0.00-0.78; P<0.001) had a lower incidence of overall adverse events (AEs).
CONCLUSION
Pembrolizumab plus lenvatinib and pembrolizumab plus axitinib resulted in the highest PFS and OS rates, respectively. Pembrolizumab plus axitinib may be the best option when AEs are a concern.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com/, identifier INPLASY202410078.
背景
尽管免疫检查点抑制剂（ICIs）在整体生存方面显示出明显优于标准晚期肾细胞癌（aRCC）治疗的优势，但这些药物对肿瘤的反应仍然很差。一些研究表明，包括 ICI 的联合治疗似乎是最佳治疗方法；然而，在疗效和毒性方面的整体获益仍需要评估。因此，我们进行了一项网络荟萃分析，以评估几种包含 ICI 的联合治疗方案的疗效差异，为临床治疗选择提供依据。
方法
我们对 PubMed、EMBASE 和 Cochrane 图书馆自 2010 年 1 月至 2023 年 6 月的文献进行了全面检索。使用 R 4.4.2 和 STATA 16.0 分析数据；风险比（HR）和优势比（OR）及其 95%置信区间（CI）用于评估结果。
结果
间接比较显示，纳武利尤单抗联合卡博替尼和帕博利珠单抗联合仑伐替尼在无进展生存期（PFS）方面是最有效的治疗方法，两种干预措施之间没有显著差异（HR，1.31；95%CI，0.96-1.78；P=0.08）；秩概率显示，帕博利珠单抗联合仑伐替尼有 57.1%的可能性成为首选治疗方法。在没有帕博利珠单抗联合阿昔替尼、纳武利尤单抗联合伊匹单抗、avelumab 联合阿昔替尼、纳武利尤单抗联合卡博替尼和帕博利珠单抗联合仑伐替尼之间的间接比较的情况下，帕博利珠单抗联合阿昔替尼（40.2%）是总体生存（OS）的最佳治疗选择。与帕博利珠单抗联合仑伐替尼相比，纳武利尤单抗联合伊匹单抗（OR，0.07；95%CI，0.01-0.65；P=0.02）和帕博利珠单抗联合阿昔替尼（OR，0.05；95%CI，0.00-0.78；P<0.001）的总体不良事件（AE）发生率更低。
结论
帕博利珠单抗联合仑伐替尼和帕博利珠单抗联合阿昔替尼分别导致了最高的 PFS 和 OS 率。当关注 AE 时，帕博利珠单抗联合阿昔替尼可能是最佳选择。
系统评价注册
https://inplasy.com/，标识符 INPLASY202410078。
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