Efficacy and Safety of Lenvatinib Plus Everolimus in Metastatic Renal Cell Carcinoma After Immune Checkpoint and VEGFR Tyrosine Kinase Inhibitors Treatment.

Abstract

Purpose: Real-world data on the efficacy and safety of lenvatinib plus everolimus in metastatic renal cell carcinoma (RCC) after failure of immune checkpoint inhibitors (ICIs) and/or VEGFR-targeted tyrosine kinase inhibitors (TKIs) remain limited.

Materials and methods: This single-center retrospective study included patients with metastatic RCC treated with lenvatinib plus everolimus as second-line or later therapy at Asan Medical Center, Korea, between September 2017 and June 2024. Data on dose adjustments, treatment response, survival, and adverse events were collected from electronic medical records. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS); secondary endpoints included overall survival (OS), time to progression (TTP), adverse events, and prognostic factors.

Results: A total of 83 patients were included, predominantly with clear cell histology (90.4%). The median number of prior therapies was four (range, 1-7), with 80.7% receiving the combination as fourth-line or beyond. All had prior anti-angiogenic TKI exposure, 86.7% had received ICIs, and 37.3% had prior mTOR inhibitor therapy. The ORR was 40.0%, with disease control at 81.3%. Median PFS and OS were 5.4 months (95% CI, 4.4-6.8) and 8.5 months (95% CI, 6.3-12.1), respectively. Efficacy was consistent across key subgroups. During the treatment, lenvatinib dose reductions were required in 55.4% of patients, and 26.5% experienced treatment interruptions. Grade ≥3 proteinuria occurred in 22.9%.

Conclusion: Lenvatinib plus everolimus demonstrated promising efficacy in heavily pretreated patients with metastatic RCC, including those previously exposed to VEGFR-targeted TKIs and/or ICIs. Further studies are warranted to optimize treatment strategies in this patient population.