biostudies-literaturePhadnis SNCATS NIH HHSNCI NIH HHS101609https://www.ebi.ac.uk/biostudies/studies/S-EPMC10774869biostudies-literatureUnknown8(6)<h4>Background</h4>Combined use of inhibitors of mammalian target of rapamycin (mTOR) and vascular endothelial growth factor (VEGF-2) receptors is a potential strategy to overcome resistance to either class of drugs when used alone.<h4>Patients and methods</h4>We designed a phase 1 trial to test the drug combination of a multikinase VEGF receptor 2 inhibitor, vandetanib, and an mTOR inhibitor, everolimus, in a pediatric and young adult patient cohort with advanced cancers. Exceptional responders were probed for tumor mutational profile to explore possible molecular mechanisms of response.<h4>Results</h4>Among 21 enrolled patients, clinical benefit was observed in 38% (one patient with partial response and eight patients with stable disease) with a median progression-free survival of 3.3 moESMO openEverolimus in combination with vandetanib in children, adolescents, and young adults: a phase I study.PMC10774869U01 CA180964P30 CA016672UL1 TR000371R01 CA273168R01 CA242845Meric-Bernstam FGorlick RSubbiah VSubbiah IMAmini BDaw NCPhadnis SPiha-Paul SAZaky WGouda MAHerzog CEMorani ACSchwartz CLWang XHarrison DJfalseEverolimus in combination with vandetanib in children, adolescents, and young adults: a phase I study.<h4>Background</h4>Combined use of inhibitors of mammalian target of rapamycin (mTOR) and vascular endothelial growth factor (VEGF-2) receptors is a potential strategy to overcome resistance to either class of drugs when used alone.<h4>Patients and methods</h4>We designed a phase 1 trial to test the drug combination of a multikinase VEGF receptor 2 inhibitor, vandetanib, and an mTOR inhibitor, everolimus, in a pediatric and young adult patient cohort with advanced cancers. Exceptional responders were probed for tumor mutational profile to explore possible molecular mechanisms of response.<h4>Results</h4>Among 21 enrolled patients, clinical benefit was observed in 38% (one patient with partial response and eight patients with stable disease) with a median progression-free survival of 3.3 mo2023-01-01T00:00:00Z2023 Dec2026-06-01T17:18:50.356Z2024-11-14T02:57:32.152ZS-EPMC107748693787923310.1016/j.esmoop.2023.101609