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Ref Type Journal Article
PMID (24714778)
Authors Judson I, Scurr M, Gardner K, Barquin E, Marotti M, Collins B, Young H, Jürgensmeier JM, Leahy M
Title Phase II study of cediranib in patients with advanced gastrointestinal stromal tumors or soft-tissue sarcoma.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 20
Issue 13
Date 2014 Jul 01
URL
Abstract Text Cediranib is a potent VEGF signaling inhibitor with activity against all three VEGF receptors and KIT. This phase II study evaluated the antitumor activity of cediranib in patients with metastatic gastrointestinal stromal tumor (GIST) resistant/intolerant to imatinib, or metastatic soft-tissue sarcomas (STS; ClinicalTrials.gov, NCT00385203).Patients received cediranib 45 mg/day. Primary objective was to determine the antitumor activity of cediranib according to changes in 2[18F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)FDG-PET) tumor uptake in patients with GIST using maximum standardized uptake values (SUVmax). Secondary objectives included objective tumor response and tolerability in patients with GIST/STS.Thirty-four of 36 enrolled patients were treated (GIST n = 24; STS n = 10). At day 29, five patients had confirmed decreases in SUVmax (≥10% from day 8) and two had confirmed partial metabolic responses (≥25% decrease), but arithmetic mean percentage changes in SUVmax, averaged across the cohort, were not significant at day 8 [6.8%; 95% confidence interval (CI), 19.95-33.54) or day 29 (4.6%; 95% CI, 8.05-17.34). Eleven patients with GIST achieved a best objective tumor response of stable disease; eight achieved stable disease ≥16 weeks. In patients with STS, four of six with alveolar soft-part sarcoma (ASPS) achieved confirmed and durable partial responses. The commonest adverse events were diarrhea (85%), fatigue (74%), and hypertension (68%).In patients progressing on imatinib/sunitinib, cediranib 45 mg/day demonstrated evidence of activity by (18)FDG-PET, but did not reduce average SUVmax. Evidence of antitumor activity was seen in ASPS.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Cediranib AZD-2171|Recentin|AZD2171|AZD 2171 KIT Inhibitor 50 VEGFR1 Inhibitor 5 VEGFR2 Inhibitor 35 VEGFR3 Inhibitor 5 Cediranib (AZD-2171) is an ATP-competitive inhibitor of all three vascular endothelial growth factor receptors (FLT1, KDR, and FLT4) and KIT, thereby blocking VEGF-signaling, angiogenesis, and tumor cell growth (PMID: 15899831, PMID: 24714778, PMID: 32444417).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown gastrointestinal stromal tumor not applicable Cediranib Phase II Actionable In a Phase II trial, treatment with Cediranib (AZD-2171) resulted in stable disease as best response in 55% (11/20) gastrointestinal stromal tumor patients, with 8 patients achieving stable disease for greater than or equal to 16 weeks (PMID: 24714778). 24714778