Activity of sunitinib in extraskeletal myxoid chondrosarcoma

作者：Stacchiotti S^*; Pantaleo M A; Astolfi A; Dagrada G P; Negri T; Tos A P Dei; Indio V; Morosi C; Gronchi A; Colombo C; Conca E; Toffolatti L; Tazzari M; Crippa F; Maestro R; Pilotti S; Casali P G

来源：European Journal of Cancer, 2014, 50(9): 1657-1664.

DOI：10.1016/j.ejca.2014.03.013

• Sarcoma
• Extraskeletal myxoid chondrosarcoma
• Chondrosarcoma
• Sunitinib
• Antiangiogenic
• Chemotherapy

Background: Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma, marked by NR4A3 rearrangement. Herein we report on the activity of sunitinib in a series of 10 patients, strengthening what initially observed in two cases.
Patients and methods: From July 2011, 10 patients with progressive metastatic translocated EMC have been consecutively treated with sunitinib 37.5 mg/day, on a named-use basis. In an attempt to interpret the activity of sunitinib in EMC, genotype/phenotype correlations were carried out by fluorescence in situ hybridization (FISH) analyses. Moreover, transcriptome, immunohistochemical and biochemical analyses of a limited set of samples were performed focusing on some putative targets of sunitinib.
Results: Eight of 10 patients are still on therapy. Six patients had a Response Evaluation Criteria in Solid Tumours (RECIST) partial response (PR), two were stable, two progressed. Positron emission tomography (PET) was consistent in 6/6 evaluable cases. One patient underwent surgery after sunitinib, with evidence of a pathologic response. At a median follow-up of 8.5 months (range 2-28), no secondary resistance was detected. Median progression free survival (PFS) has not been reached. Interestingly, all responsive cases turned out to express the typical EWSR1-NR4A3 fusion, while refractory cases carried the alternative TAF15-NR4A3 fusion. Among putative sunitinib targets, only RET was expressed and activated in analysed samples.
Conclusions: This report confirms the therapeutic activity of sunitinib in EMC. Genotype/phenotype analyses support a correlation between response and EWSR1-NR4A3 fusion. Involvement of RET deserves further investigation.

• 出版日期2014-6