Results from the LenCabo Phase II trial presented at the European Society for Medical Oncology (ESMO) Congress 2025 demonstrate that a dual targeted therapy combination significantly improved outcomes for patients with metastatic clear-cell renal carcinoma (ccRCC) whose disease progressed following immunotherapy. The study, led by researchers from The University of Texas MD Anderson Cancer Center, represents the first randomized head-to-head comparison of two commonly used second-line treatments in this patient population.
Trial Design and Patient Population
The randomized Phase II trial enrolled 90 patients with metastatic or advanced ccRCC who had previously received one or two treatments, including at least one immunotherapy targeting PD-1 or PD-L1. Patients were randomized to receive either the combination of lenvatinib and everolimus or cabozantinib monotherapy as second-line treatment.
Superior Progression-Free Survival Outcomes
The study revealed significant differences in treatment efficacy between the two arms. Patients treated with lenvatinib plus everolimus achieved a median progression-free survival (PFS) of 15.7 months compared to 10.2 months for those receiving cabozantinib. Additionally, 62.5% of patients in the combination therapy group experienced cancer progression compared to 76% of those who received cabozantinib.
"This is the first randomized trial to directly compare these two commonly used second-line treatments," said Andrew W. Hahn, M.D., assistant professor of Genitourinary Medical Oncology at MD Anderson Cancer Center, who presented the data. "These findings offer insights into treatment sequencing and the importance of generating head-to-head data to guide clinical decisions."
Clinical Context and Treatment Landscape
Current first-line treatment for patients with metastatic ccRCC consists of immune checkpoint inhibitors, sometimes combined with targeted therapies. When cancer stops responding to these initial treatments, the next treatment options include lenvatinib and everolimus combination therapy or cabozantinib monotherapy.
The trial was specifically designed to evaluate the comparative efficacy of these second-line therapies to identify the regimen that provides longer PFS and improved patient outcomes. The findings suggest that lenvatinib plus everolimus may offer a more meaningful benefit as second-line treatment and may guide future treatment selection for patients in need.
Implications for Clinical Practice
These results provide the first direct comparative evidence between two standard second-line treatment options for patients with advanced kidney cancer who have experienced disease progression following immunotherapy. The superior progression-free survival demonstrated with the lenvatinib-everolimus combination offers clinicians valuable data to inform treatment decisions in this challenging patient population.
