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Updated: Jul 12, 2025

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Everolimus in combination with vandetanib in children, adolescents, and young adults: a phase I study

S Phadnis1, X Wang2, N C Daw3

  • 1Division of Pediatrics, Children's of Alabama at The University of Alabama, Birmingham.

ESMO Open
|October 25, 2023
PubMed
Abstract

Insights

The combination of vandetanib and everolimus demonstrated early activity and a tolerable safety profile in pediatric patients with advanced cancers. This approach may help overcome resistance to single-agent therapies.

Area of Science:

  • Oncology
  • Pharmacology
  • Pediatric Medicine

Background:

  • Resistance to single-agent mammalian target of rapamycin (mTOR) or vascular endothelial growth factor receptor 2 (VEGF-2) inhibitors is a clinical challenge.
  • Combined inhibition of mTOR and VEGF-2 pathways is a potential strategy to overcome drug resistance.

Purpose of the Study:

  • To evaluate the safety and preliminary efficacy of combining vandetanib (VEGF-2 inhibitor) and everolimus (mTOR inhibitor) in pediatric and young adult patients with advanced cancers.
  • To explore molecular mechanisms of response in exceptional responders.

Main Methods:

  • A Phase 1 clinical trial was conducted.
  • The study enrolled a cohort of pediatric and young adult patients with advanced cancers.
  • Tumor mutational profiles of exceptional responders were analyzed.

Main Results:

  • Clinical benefit was observed in 38% of 21 enrolled patients (1 partial response, 8 stable disease).
  • Median progression-free survival was 3.3 months.
  • The most common adverse event was rash; no dose-limiting toxicities were observed. Genetic alterations were identified in exceptional responders.

Conclusions:

  • The combination of vandetanib and everolimus demonstrated early clinical activity in pediatric patients with advanced cancers.
  • The drug combination exhibited a tolerable toxicity profile.
  • This combination therapy represents a promising strategy for advanced pediatric cancers.
Keywords:
everolimuspediatricsphase I trialsarcomavandetanib

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