Internal Medicine Department, Shaoxing Yuecheng People's Hospital, Shaoxing City, Zhejiang Province, China.
Department of Radiotherapy, Shaoxing People's Hospital, Shaoxing, Zhejiang, China.
Medicine (Baltimore). 2024 May 31;103(22):e38329. doi: 10.1097/MD.0000000000038329.
To date, no meta-analysis has been conducted to compare the effectiveness and safety of adjuvant tyrosine kinase inhibitors (TKIs) and adjuvant immunotherapies (IMTs) in renal cell carcinoma (RCC) patients using reconstructed individual patient data (IPD). This study aims to fill that gap by assessing the efficacy and safety profiles of these treatments in such patients.
This study employed a systematic approach for identifying relevant literature from the PubMed and EMBASE databases. We included articles published in English from the inception of these databases until November 11, 2023, focusing specifically on appropriate phase III randomized controlled trials (RCTs). To reconstruct survival curves, we utilized a semiautomated tool, WebPlotDigitizer, in conjunction with a novel shiny application integrated with R software. For adverse events (AEs), the summary measures were incidences, expressed as a 95% confidence interval (CI), calculated using a random-effects model with a logit transformation.
The analysis included 8 RCTs with a total of 9119 patients. Compared to adjuvant TKIs, adjuvant IMTs showed a similar disease-free survival (DFS) (hazard ratio [HR] 1.03, 95% CI [0.98-1.09], P = .281). However, the overall survival (OS) rates between the 2 groups couldn't be directly compared due to unmatched control groups in the IMT and TKI studies. Against placebo, adjuvant IMTs demonstrated superior DFS (HR 0.82, 95% CI [0.71-0.94], P = .004) but comparable OS (HR 0.79, 95% CI [0.59-1.06], P = .120). Against placebo, adjuvant TKIs showed superior DFS (HR 0.85, 95% CI [0.79-0.92], P < .0001) and marginally better OS (HR 0.89, 95% CI [0.80-0.996], P = .042). Regarding severe AEs and discontinuation rates due to AEs, adjuvant IMTs had a significantly lower incidence of severe AEs (25% [320/1282] vs 59% [2192/3716], odds ratio [OR] 0.23, 95% CI [0.20-0.27], P < .0001) and a markedly better discontinuation rate (39% [499/1282] vs 52% [2068/4018], OR 0.60, 95% CI [0.53-0.68], P < .0001) compared to TKIs.
This paper presents a thorough analysis of DFS, OS, and treatment-related AEs across various groups in RCC patients, offering a valuable resource for clinicians in everyday practice. Our findings indicate that while adjuvant IMTs and adjuvant TKIs demonstrate similar DFS, IMTs are notably superior in terms of safety and compliance.
迄今为止，尚无荟萃分析比较肾细胞癌（RCC）患者使用重建的个体患者数据（IPD）的辅助酪氨酸激酶抑制剂（TKI）和辅助免疫疗法（IMT）的有效性和安全性。本研究旨在通过评估这些治疗方法在这些患者中的疗效和安全性特征来填补这一空白。
本研究采用系统方法从 PubMed 和 EMBASE 数据库中识别相关文献。我们纳入了从这些数据库成立到 2023 年 11 月 11 日发表的英文文章，重点是适当的 III 期随机对照试验（RCT）。为了重建生存曲线，我们使用了半自动工具 WebPlotDigitizer，并结合了一个新的闪亮应用程序，该应用程序集成了 R 软件。对于不良事件（AE），汇总指标为发生率，以 95%置信区间（CI）表示，使用对数转换的随机效应模型计算。
该分析包括 8 项 RCT，共 9119 名患者。与辅助 TKI 相比，辅助 IMT 显示出相似的无病生存率（DFS）（风险比[HR]1.03，95%CI[0.98-1.09]，P=0.281）。然而，由于 IMT 和 TKI 研究中的对照组不匹配，两组之间的总生存率（OS）无法直接比较。与安慰剂相比，辅助 IMT 显示出更好的 DFS（HR 0.82，95%CI[0.71-0.94]，P=0.004），但 OS 相似（HR 0.79，95%CI[0.59-1.06]，P=0.120）。与安慰剂相比，辅助 TKI 显示出更好的 DFS（HR 0.85，95%CI[0.79-0.92]，P<0.0001）和略微更好的 OS（HR 0.89，95%CI[0.80-0.996]，P=0.042）。关于严重 AE 和因 AE 而停药率，辅助 IMT 发生严重 AE 的发生率明显较低（25%[320/1282]与 59%[2192/3716]，比值比[OR]0.23，95%CI[0.20-0.27]，P<0.0001），停药率明显更好（39%[499/1282]与 52%[2068/4018]，OR 0.60，95%CI[0.53-0.68]，P<0.0001）与 TKI 相比。
本文全面分析了 RCC 患者不同组别的 DFS、OS 和与治疗相关的 AE，为临床医生日常实践提供了有价值的资源。我们的研究结果表明，尽管辅助 IMT 和辅助 TKI 显示出相似的 DFS，但 IMT 在安全性和依从性方面明显更优。
