Phase II study of cediranib in patients with advanced gastrointestinal stromal tumors or soft-tissue sarcoma.
OBJECTIVE
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).


METHODS
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.


RESULTS
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%).


CONCLUSIONS
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.
Authors' Affiliations: Royal Marsden Hospital, London; Ian.Judson@icr.ac.uk.
Ian
I
Judson
Authors' Affiliations: Royal Marsden Hospital, London;
Michelle
M
Scurr
Authors' Affiliations: Royal Marsden Hospital, London;
Kate
K
Gardner
Authors' Affiliations: Royal Marsden Hospital, London;
Elizabeth
E
Barquin
AstraZeneca, Macclesfield; and.
Marcelo
M
Marotti
AstraZeneca, Macclesfield; and.
Barbara
B
Collins
AstraZeneca, Macclesfield; and.
Helen
H
Young
AstraZeneca, Macclesfield; and.
Juliane M
JM
Jürgensmeier
Christie Hospital NHS Foundation Trust, Manchester, United Kingdom.
Michael
M
Leahy
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012509:Sarcoma / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology* / Q000628:therapy; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D007211:Indoles
D000970:Antineoplastic Agents; D015415:Biomarkers; D019788:Fluorodeoxyglucose F18; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C500926:cediranib; D007211:Indoles