Mayo Clinic, Phoenix, AZ, USA.
Mayo Clinic, Rochester, MN, USA.
Eur Urol. 2021 Dec;80(6):712-723. doi: 10.1016/j.eururo.2021.03.016. Epub 2021 Apr 3.
Identifying the most effective first-line treatment for metastatic renal cell carcinoma (mRCC) is challenging as rapidly evolving data quickly outdate the existing body of evidence, and current approaches to presenting the evidence in user-friendly formats are fraught with limitations.
To maintain living evidence for contemporary first-line treatment for previously untreated mRCC.
We have created a living, interactive systematic review (LISR) and network meta-analysis for first-line treatment of mRCC using data from randomized controlled trials comparing contemporary treatment options with single-agent tyrosine kinase inhibitors. We applied an advanced programming and artificial intelligence-assisted framework for evidence synthesis to create a living search strategy, facilitate screening and data extraction using a graphical user interface, automate the frequentist network meta-analysis, and display results in an interactive manner.
As of October 22, 2020, the LISR includes data from 14 clinical trials. Baseline characteristics are summarized in an interactive table. The cabozantinib + nivolumab combination (CaboNivo) is ranked the highest for the overall response rate, progression-free survival, and overall survival, whereas ipilimumab + nivolumab (NivoIpi) is ranked the highest for achieving a complete response (CR). NivoIpi, and atezolizumab + bevacizumab (AteBev) were ranked highest (lowest toxicity) and CaboNivo ranked lowest for treatment-related adverse events (AEs). Network meta-analysis results are summarized as interactive tables and plots, GRADE summary-of-findings tables, and evidence maps.
This innovative living and interactive review provides the best current evidence on the comparative effectiveness of multiple treatment options for patients with untreated mRCC. Trial-level comparisons suggest that CaboNivo is likely to cause more AEs but is ranked best for all efficacy outcomes, except NivoIpi offers the best chance of CR. Pembrolizumab + axitinib and NivoIpi are acceptable alternatives, except NivoIpi may not be preferred for patients with favorable risk. Although network meta-analysis provides rankings with statistical adjustments, there are inherent biases in cross-trial comparisons with sparse direct evidence that does not replace randomized comparisons.
It is challenging to decide the best option among the several treatment combinations of immunotherapy and targeted treatments for newly diagnosed metastatic kidney cancer. We have created interactive evidence summaries of multiple treatment options that present the benefits and harms and evidence certainty for patient-important outcomes. This evidence is updated as soon as new studies are published.
由于快速发展的数据迅速使现有证据过时，因此确定转移性肾细胞癌（mRCC）的最佳一线治疗方法极具挑战性，而目前以用户友好的格式呈现证据的方法存在诸多局限性。
为保持对未经治疗的 mRCC 的当代一线治疗的最新循证医学证据。
我们创建了一个针对 mRCC 一线治疗的交互式、实时系统评价（LISR）和网络荟萃分析，使用了来自比较当代治疗方案与单药酪氨酸激酶抑制剂的随机对照试验的数据。我们应用了一个先进的编程和人工智能辅助框架来进行证据综合，以创建一个实时搜索策略，使用图形用户界面促进筛选和数据提取，自动化了似然比网络荟萃分析，并以交互式方式显示结果。
截至 2020 年 10 月 22 日，LISR 纳入了来自 14 项临床试验的数据。基线特征总结在一个交互式表格中。卡博替尼+纳武单抗（CaboNivo）组合在总缓解率、无进展生存期和总生存期方面排名最高，而伊匹单抗+纳武单抗（NivoIpi）在实现完全缓解（CR）方面排名最高。NivoIpi 和阿替利珠单抗+贝伐珠单抗（AteBev）在毒性方面排名最高（最低），而卡博替尼（CaboNivo）在治疗相关不良反应（AE）方面排名最低。网络荟萃分析结果总结为交互式表格和图表、GRADE 发现总结表和证据图谱。
这项创新的实时和交互式综述提供了有关未经治疗的 mRCC 患者多种治疗选择的比较效果的最佳最新证据。试验层面的比较表明，卡博替尼（CaboNivo）可能会引起更多的不良反应，但在所有疗效结果方面均排名最佳，除了伊匹单抗+纳武单抗（NivoIpi）可提供最佳的 CR 机会。帕博利珠单抗+阿昔替尼和伊匹单抗+纳武单抗（NivoIpi）是可接受的替代方案，除了 NivoIpi 可能不适合风险良好的患者。虽然网络荟萃分析提供了具有统计调整的排名，但由于稀疏的直接证据存在交叉试验比较的固有偏倚，因此无法替代随机对照试验。
对于新诊断的转移性肾细胞癌的多种免疫治疗和靶向治疗组合方案，很难做出最佳选择。我们创建了多个治疗方案的交互式证据总结，展示了对患者重要结局的获益和危害以及证据确定性。一旦发表了新的研究，就会更新这些证据。
