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.
To compare long-term responders of these trials using extended follow-up data stratified by International Metastatic RCC Database Consortium risk group.
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.
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).
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.
Kidney cancer (Clifton, Va.). 2025 Feb 04 [Epub]
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
Division of Solid Tumor Oncology, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA., School of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, Philadelphia, PA, USA., Department of Urology, New York-Presbyterian Hospital, Weill Cornell Medicine, New York, NY, USA., Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Case Western Reserve University, Cleveland, OH, USA., Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA., Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA., Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/40589703