Activity of lenvatinib-based therapy in previously treated patients with metastatic renal cell carcinoma: A European multicenter study (LENVA-LAT)

Eur J Cancer. 2025 May 2:220:115389. doi: 10.1016/j.ejca.2025.115389. Epub 2025 Mar 26.

Abstract

Background and objective: Lenvatinib's activity after immune checkpoint inhibitors (ICI) combination therapy in renal cell carcinoma (RCC) remains unknown. We aimed to describe the real-world outcomes of patients with metastatic RCC (mRCC) treated with lenvatinib after failure of the prior standard of care.

Methods: Multicenter retrospective study including patients with mRCC treated with lenvatinib-based therapies beyond first-line therapy between 2020 and 2024. The primary endpoints were objective response rate (ORR) and time-to-treatment failure (TTF). Secondary endpoints included disease control rate (DCR), overall survival (OS), and safety.

Results: We included 133 patients, with a median age of 61 years. Clear-cell was the main subtype (82.0 %). Before lenvatinib treatment, 15.8 %, 51.9 %, and 27.8 % of patients showed favorable, intermediate, and poor risk disease, respectively, according to the International Metastatic RCC Database Consortium (IMDC). Moreover, patients received a median of 3 previous lines of treatment, including ICIs (90.2 %) and cabozantinib (90.2 %). Lenvatinib was given alone (45.9 %) or in combination with everolimus (33.8 %), pembrolizumab (18.0 %) or investigational agents (2.3 %). The ORR and DCR were 29.1 % and 67.7 %, respectively, with no differences between regimens or lines of treatment. With a median follow-up time of 13.5 months, the median TTF and OS were 6.2 and 9.6 months. Toxicity was manageable with dose modifications required in 34.6 %. The discontinuation rate was 9.8 %, with one toxic death.

Conclusion: Lenvatinib-based regimens were active and safe for heavily pre-treated patients with mRCC. These findings provide evidence to support its use in daily practice.

Keywords: Efficacy; Kidney cancer; Later lines; Lenvatinib; Outcomes; Real-world data; Renal Cell Carcinoma; Safety.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Carcinoma, Renal Cell* / drug therapy
  • Carcinoma, Renal Cell* / mortality
  • Carcinoma, Renal Cell* / pathology
  • Carcinoma, Renal Cell* / secondary
  • Europe
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Kidney Neoplasms* / drug therapy
  • Kidney Neoplasms* / mortality
  • Kidney Neoplasms* / pathology
  • Male
  • Middle Aged
  • Phenylurea Compounds* / administration & dosage
  • Phenylurea Compounds* / adverse effects
  • Phenylurea Compounds* / therapeutic use
  • Protein Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors* / therapeutic use
  • Quinolines* / administration & dosage
  • Quinolines* / adverse effects
  • Quinolines* / therapeutic use
  • Retrospective Studies
  • Treatment Outcome

Substances

  • lenvatinib
  • Phenylurea Compounds
  • Quinolines
  • Protein Kinase Inhibitors
  • Immune Checkpoint Inhibitors