The combination of lenvatinib and everolimus significant improved progression-free survival compared with cabozantinib in patients with metastatic clear cell renal cell carcinoma (ccRCC) that has progressed on PD-1 immune checkpoint inhibitors, according to findings from the phase II LenCabo trial that were presented at the European Society for Medical Oncology (ESMO) Congress 2025 (Abstract LBA94).
“This is the first randomized trial to directly compare these two commonly used second-line treatments,” said lead author Andrew W. Hahn, MD, Assistant Professor of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center. “These findings offer insights into treatment sequencing and the importance of generating head-to-head data to guide clinical decisions.”
Study Design
The multicenter, randomized phase II LenCabo trial was designed to compare second-line or later treatments of lenvatinib plus everolimus or cabozantinib head to head among patients with metastatic ccRCC. All patients in the study had received one to two prior lines of treatment, including PD-1 immune checkpoint inhibition.
Key Study Findings
Patients were followed for a median of 20 months, when the median progression-free survival was 15.7 months in the lenvatinib/everolimus arm vs 10.2 months in the cabozantinib arm (hazard ratio [HR] = 0.51; 95% confidence interval [CI] = 0.29–0.89; P = .02). The objective response rate was 52.6% with lenvatinib and everolimus vs 38.6% with cabozantinib. Overall survival data were still immature at the time of data cutoff.
No treatment-related deaths were reported in the trial.
Disclosure: The study was supported in part by the National Cancer Institute, MD Anderson's Prometheus Informatics system, and the Department of Genitourinary Medical Oncology's Eckstein and Alexander Laboratories. For full disclosures of the study authors, visit ctimeetingtech.com/esmo2025.
