lenvatinib

Overview

Lenvatinib is a multi-kinase inhibitor targeting VEGFR1-3, FGFR1-4, PDGFRa, KIT, and RET, with FDA approvals in hepatocellular carcinoma, thyroid cancer, renal cell carcinoma, and endometrial carcinoma (in combination with pembrolizumab for MSS/pMMR disease).

Evidence in the corpus

  • Lenvatinib in combination with pembrolizumab is an FDA-approved regimen for MSS/pMMR endometrial carcinoma; Black EC patients are enriched for this pMMR/MSS subtype (69% of Black ECs were CN-H/TP53abn), potentially making lenvatinib+pembrolizumab the applicable regimen for a larger proportion of Black than White EC patients PMID:37651310.
  • ERBB2 amplification, enriched in Black EC patients (12% vs 3%), represents an alternative target that may partly explain why fewer Black patients are eligible for standard dMMR-targeting agents like dostarlimab, shifting the therapeutic landscape toward anti-HER2 and lenvatinib-based strategies PMID:37651310.
  • In a PDTO functional screen of 92 sarcoma specimens, tumors with prior systemic therapy were more sensitive to lenvatinib than treatment-naïve specimens (p=0.011), suggesting that prior treatment may induce adaptive dependence on VEGFR/FGFR signaling PMID:39305899.
  • Lenvatinib+pembrolizumab combination data were not available in the HiTME training cohorts; cited as a limitation for the ccRCC IO/TKI decision-tree model PMID:22138691
  • High FGFR3 expression/gain guided lenvatinib consideration in metastatic NEN patients (PN1, PN14, PN17, PN25) in the POG NEN WGTA cohort (n=28) PMID:24326773
  • First-line HCC: REFLECT trial — lenvatinib non-inferior to sorafenib, median OS 13.6 vs 12.3 months (HR 0.92, 95% CI 0.79–1.06); mRECIST ORR 24.1% (investigator) / 40.6% (masked review); approved as alternative first-line for Child–Pugh A, BCLC-C patients (except main portal vein thrombosis or >50% liver involvement) PMID:24798001

Resistance mechanisms

  • Not directly characterized in the corpus.

Cancer types (linked)

  • UCEC
  • Sarcoma (various histologies — functional screen, treatment-experienced specimens)

Sources

This page was processed by crosslinker on 2026-05-09. - PMID:22138691

This page was processed by crosslinker on 2026-05-09. - PMID:24326773

This page was processed by crosslinker on 2026-05-09. - PMID:24798001

This page was processed by wiki-cli on 2026-05-11.