Laukhtina Ekaterina, Quhal Fahad, Mori Keiichiro, Sari Motlagh Reza, Rajwa Pawel, Yanagisawa Takafumi, Mostafaei Hadi, König Frederik, Aydh Abdulmajeed, Pradere Benjamin, Enikeev Dmitry, Karakiewicz Pierre I, Schmidinger Manuela, Shariat Shahrokh F
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia.
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia.
Eur Urol Oncol. 2022 Feb;5(1):120-124. doi: 10.1016/j.euo.2021.12.007. Epub 2022 Jan 3.
We determined the oncologic outcomes and safety profiles of adjuvant immune checkpoint inhibitors (ICIs) compared to adjuvant tyrosine kinase inhibitors (TKIs) in patients at high risk after nephrectomy for clinically nonmetastatic renal cell carcinoma (RCC). Network meta-analyses were conducted for disease-free survival (DFS), overall survival (OS), and adverse events (AEs) with placebo as the common comparator arm. Six trials (KEYNOTE-564, S-TRAC, ASSURE, PROTECT, ATLAS, and SORCE) were included in our analysis. Compared to placebo, both pembrolizumab (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.51-0.92) and pazopanib 800 mg (HR 0.69, 95% CI 0.49-0.97) were significantly associated with better DFS. Adjuvant pembrolizumab (HR 0.54, 95% CI 0.30-0.97) was significantly associated with better OS compared to TKIs (HR 0.93, 95% CI 0.83-1.04). Analysis of treatment ranking revealed that pembrolizumab was the best treatment with regard to both DFS and OS and had the lowest likelihood of any-grade and high-grade AEs in comparison to TKIs. The superior oncologic benefit of pembrolizumab and its better toxicity profile support it as the new standard of care in the adjuvant setting for nephrectomy patients at high risk of RCC relapse. PATIENT SUMMARY: For patients with kidney cancer at high risk of relapse after surgical removal of their kidney, postoperative therapy with the immune checkpoint inhibitor pembrolizumab offers the best risk/benefit ratio.
我们比较了辅助性免疫检查点抑制剂（ICI）与辅助性酪氨酸激酶抑制剂（TKI）在临床非转移性肾细胞癌（RCC）肾切除术后高危患者中的肿瘤学结局和安全性。以安慰剂作为共同对照臂，对无病生存期（DFS）、总生存期（OS）和不良事件（AE）进行了网状荟萃分析。我们的分析纳入了六项试验（KEYNOTE-564、S-TRAC、ASSURE、PROTECT、ATLAS和SORCE）。与安慰剂相比，帕博利珠单抗（风险比[HR]0.68，95%置信区间[CI]0.51-0.92）和800mg帕唑帕尼（HR 0.69，95%CI 0.49-0.97）均与更好的DFS显著相关。与TKI（HR 0.93，95%CI 0.83-1.04）相比，辅助性帕博利珠单抗（HR 0.54，95%CI 0.30-0.97）与更好的OS显著相关。治疗排名分析显示，与TKI相比，帕博利珠单抗在DFS和OS方面都是最佳治疗方法，且任何级别和高级别AE的发生可能性最低。帕博利珠单抗卓越的肿瘤学获益及其更好的毒性特征支持其作为RCC复发高危肾切除患者辅助治疗的新护理标准。患者总结：对于肾切除术后复发风险高的肾癌患者，术后使用免疫检查点抑制剂帕博利珠单抗治疗具有最佳的风险/获益比。
