Phase II Study of Cediranib in Patients with Advanced Gastrointestinal Stromal Tumors or Soft-Tissue Sarcoma

Purpose: 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). Experimental Design: 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 (SUV max ). 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 SUV max (≥10% from day 8) and two had confirmed partial metabolic responses (≥25% decrease), but arithmetic mean percentage changes in SUV max , 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 SUV max . Evidence of antitumor activity was seen in ASPS. Clin Cancer Res; 20(13); 3603–12. ©2014 AACR .