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

Abstract

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 ¼ 24; STS n ¼ 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. Ó2014 AACR.

Beyond standard therapy: drugs under investigation for the treatment of gastrointestinal stromal tumor

“…Their study showed 2 confirmed PR cases and 22 patients with SD. A phase II clinical trial was conducted to assess the activity of cediranib in patients with metastatic GIST or soft-tissue sarcoma who were resistant or intolerant to IM [89]. Changes in 2[18F]fluoro-2-deoxy-D-glucose positron emission tomography ( 18 FDG-PET) were used to determine the antitumor activity of cediranib using maximum standardized uptake values (SUV max ).…”

Alveolar soft part sarcoma in children and adolescents: The European Paediatric Soft Tissue Sarcoma study group prospective trial (EpSSG NRSTS 2005)

“…While most patients require surgery with an R0 resection for local control, the high rate of metastasis would indicate systemic therapy. However, it is thought that these tumors are chemoinsensitive, but early reports have demonstrated response to antiangiogenic therapies such as cediranib, bevacizumab, and sunitinib …”

Targeted therapy for soft tissue sarcomas in adolescents and young adults

“…Cediranib is a TKI with activity against VEGFR1–3 and KIT that has been investigated in GIST and STS and caused reduced FDG-PET activity in four out of six patients with ASPS but no overall reductions in SUVmax 96. A larger Phase II prospective trial found an ORR of 35% and a disease control rate of 84% at 24 weeks in patients with ASPS treated with single-agent cediranib 97.…”