Sunitinib in advanced alveolar soft part sarcoma: evidence of a direct antitumor effect

Patients and methods: From July 2007, nine patients with progressive metastatic ASPS received sunitinib 37.5 mg/day, within a named use program. Cryopreserved material was available for five naive patients, among whom three received sunitinib. Immunofluorescence (IF)/confocal microscopy, biochemical, and molecular/cytogenetic analyses were carried out, complemented by antiproliferative and activation assays in a short-term culture derived from one case. Results: All patients were eligible for response. Best RECIST response was partial response in five cases, stable disease in three, and progression in one. The median progression-free survival was 17 months. Positron emission tomography results were consistent. Two cases of interval progressions were recorded. Antiproliferative assays and biochemistry on short-term culture showed that sunitinib is able to markedly impair ASPS cells growth and switch-off PDGFRB. IF/confocal microscopy demonstrated coexpression and physical association between PDGFRB/vascular endothelial growth factor receptor 2 (VEGFR2) and RET/VEGFR2 in ASPS cells, which was validated by biochemistry. PDGFRB, RET, and MET ligand-dependent activation was confirmed. Conclusions: We confirm the clinical efficacy of sunitinib in ASPS, mediated by PDGFRB, VEGFR2, and RET, which are all expressed in tumor cells. A direct antitumor effect was shown in a short-term cell culture.