Durable responses to immune checkpoint inhibitor-based regimens for metastatic clear cell renal cell carcinoma stratified by IMDC risk groups: A pooled analysis of four randomized phase 3 trials.

IF 1.1
Kidney cancer (Clifton, Va.) Pub Date : 2025-01-01 Epub Date: 2025-02-04 DOI:10.1177/24684570241311419
Albert Jang, Jeffrey Y Zhong, Hamsa L S Kumar, Kevin K Zarrabi, Alec Zhu, Abby L Grier, Adam Calaway, Jonathan E Shoag, Laura Bukavina, Angela Y Jia, Prateek Mendiratta, Iris Y Sheng, Santosh Rao, Jason R Brown, Jorge A Garcia, Seunghee Margevicius, Pingfu Fu, Pedro C Barata
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Abstract

Background: An immune checkpoint inhibitor (ICI) backbone is a standard of care for frontline metastatic clear cell renal cell carcinoma, involving either ICI doublet or tyrosine kinase inhibitor (TKI) with ICI. These phase 3 trials used a sunitinib control arm. The optimal regimen is uncertain.

Objective: To compare long-term responders of these trials using extended follow-up data stratified by International Metastatic RCC Database Consortium risk group.

Methods: Phase 3 trial data (CheckMate 214, KEYNOTE-426, CheckMate 9ER, and CLEAR) with a minimum follow-up of four years was used. Pseudo individual patient data (IPD) was obtained from Kaplan-Meier curves using the graph digitizer software IPDfromKM R package to extract coordinates of points on the curves and to apply a numerical algorithm to reconstruct progression-free survival (PFS) and overall survival (OS) results. Durable response (DR) was defined as PFS ≥ 24 months, extreme durable response (EDR) as PFS ≥ 36 months, and long-term OS as OS ≥ 48 months.

Results: For the favorable risk group, lenvatinib-pembrolizumab had the highest DR and EDR, while ipilimumab-nivolumab had the lowest DR, and cabozantinib-nivolumab had the lowest EDR; there was no difference in long-term OS among the regimens (p = 0.11). For the intermediate/poor risk group, lenvatinib-pembrolizumab also had the highest DR and EDR compared to other regimens with similar DR and EDR; there was also no difference in long-term OS among the regimens (p = 0.22).

Conclusion: TKI-ICI was overall associated with higher DR and EDR regardless of risk status compared to ICI doublet. Yet, OS at 48 months were similar when stratified by favorable versus intermediate/poor risk.

基于免疫检查点抑制剂的方案对转移性透明细胞肾细胞癌按IMDC风险组分层的持久反应:四项随机3期试验的合并分析
背景:免疫检查点抑制剂(ICI)骨干是一线转移性透明细胞肾细胞癌的标准治疗方案,包括ICI双重或酪氨酸激酶抑制剂(TKI)与ICI。这些3期试验使用舒尼替尼对照组。最佳方案是不确定的。目的:利用国际转移性RCC数据库联盟风险组的扩展随访数据,比较这些试验的长期应答者。方法:使用3期试验数据(CheckMate 214, KEYNOTE-426, CheckMate 9ER和CLEAR),至少随访4年。使用km R软件包中的图形数字化软件ipd从Kaplan-Meier曲线中获取伪个体患者数据(IPD),提取曲线上点的坐标,并应用数值算法重建无进展生存期(PFS)和总生存期(OS)结果。持久缓解(DR)定义为PFS≥24个月,极端持久缓解(EDR)定义为PFS≥36个月,长期OS定义为OS≥48个月。结果:在有利风险组,lenvatinib-pembrolizumab的DR和EDR最高,ipilimumab-nivolumab的DR最低,cabozantinib-nivolumab的EDR最低;两组间的长期OS无差异(p = 0.11)。对于中/低风险组,lenvatinib-pembrolizumab与其他具有类似DR和EDR的方案相比,DR和EDR也最高;两组间的长期生存期也无差异(p = 0.22)。结论:与ICI双联体相比,TKI-ICI总体上与较高的DR和EDR相关,无论其风险状态如何。然而,48个月时的OS在按有利风险与中/差风险分层时相似。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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