Cediranib for metastatic alveolar soft part sarcoma

Shivaani Kummar, Deborah Allen, Anne Monks, Eric C. Polley, Curtis D. Hose, S. Percy Ivy, Ismail B. Turkbey, Scott Lawrence, Robert J. Kinders, Peter Choyke, Richard Simon, Seth M. Steinberg, James H. Doroshow, Lee Helman

Research output: Contribution to journalArticlepeer-review

135 Scopus citations

Abstract

Purpose: Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor, for which no effective standard systemic treatment exists for patients with unresectable disease. Cediranib is a potent, oral small-molecule inhibitor of all three vascular endothelial growth factor receptors (VEGFRs). Patients and Methods: We conducted a phase II trial of once-daily cediranib (30 mg) given in 28-day cycles for patients with metastatic, unresectable ASPS to determine the objective response rate (ORR). We also compared gene expression profiles in pre- and post-treatment tumor biopsies and evaluated the effect of cediranib on tumor proliferation and angiogenesis using positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging. Results: Of 46 patients enrolled, 43 were evaluable for response at the time of analysis. The ORR was 35%, with 15 of 43 patients achieving a partial response. Twenty-six patients (60%) had stable disease as the best response, with a disease control rate (partial response + stable disease) at 24 weeks of 84%. Microarray analysis with validation by quantitative real-time polymerase chain reaction on paired tumor biopsies from eight patients demonstrated downregulation of genes related to vasculogenesis. Conclusion: In this largest prospective trial to date of systemic therapy for metastatic ASPS, we observed that cediranib has substantial single-agent activity, producing an ORR of 35% and a disease control rate of 84% at 24 weeks. On the basis of these results, an open-label, multicenter, randomized phase II registration trial is currently being conducted for patients with metastatic ASPS comparing cediranib with another VEGFR inhibitor, sunitinib.

Original languageEnglish (US)
Pages (from-to)2296-2302
Number of pages7
JournalJournal of Clinical Oncology
Volume31
Issue number18
DOIs
StatePublished - Jun 20 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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