Cediranib Is Effective in Alveolar Soft Part Sarcoma

Alveolar soft part sarcoma (ASPS) is a rare soft-tissue sarcoma that can be cured by radical surgery, but there is no effective systemic treatment for unresectable disease. Although it is a relatively indolent cancer, ASPS frequently metastasizes, and the 5-year survival rate is only 20% for patients with unresectable metastatic ASPS. Because ASPS is highly vascular, is it possible that antiangiogenic therapies may be effective in this cancer. Kummar and colleagues therefore evaluated the objective response rate of cediranib, an orally bioavailable pan-VEGFR inhibitor, in patients with unresectable metastatic ASPS in a phase II trial. Biopsies were also obtained from a subset of patients after a week of cediranib treatment to determine if gene expression changes consistent with ontarget VEGFR inhibition occurred. Of 43 evaluable patients, 15 (35%) had a partial response, including 1 patient who subsequently underwent resection and is disease-free after 16 months, and another 26 patients (60%) experienced disease stabilization. The disease control rate (partial response plus stable disease) for patients who had completed at least 6 cycles of therapy was 84%. Although dose reduction was necessary in 17 patients (40%), cediranib was generally well tolerated, with few serious adverse events. Consistent with on-target inhibition of VEGFR, the most significantly downregulated genes after cediranib treatment included genes with known roles in vasculogenesis and angiogenesis, such as angiopoietin 2, cadherin 13, and endothelial cell-specific molecule 1. These findings indicate that cediranib has single-agent activity in ASPS and support further clinical development of anti-VEGFR therapies for this cancer type. A randomized phase II study to compare the activity of cediranib with sunitinib, another VEGFR inhibitor, in advanced ASPS is ongoing.

Kummar S, Allen D, Monks A, Polley EC, Hose CD, Ivy P, et al. Cediranib for metastatic alveolar soft part sarcoma. J Clin Oncol 2013 Apr 29 [Epub ahead of print].

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