Activity of sunitinib in extraskeletal myxoid chondrosarcoma

Eur J Cancer. 2014 Jun;50(9):1657-64. doi: 10.1016/j.ejca.2014.03.013. Epub 2014 Apr 2.


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 37.5mg/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.

Keywords: Antiangiogenic; Chemotherapy; Chondrosarcoma; Extraskeletal myxoid chondrosarcoma; Sarcoma; Sunitinib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Bone Neoplasms*
  • Calmodulin-Binding Proteins / genetics
  • Chondrosarcoma / drug therapy*
  • Chondrosarcoma / genetics
  • Chondrosarcoma / secondary
  • DNA-Binding Proteins / genetics
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Rearrangement / genetics
  • Genotype
  • Humans
  • Indoles / therapeutic use*
  • Male
  • Middle Aged
  • Neoplasms, Connective and Soft Tissue / drug therapy*
  • Neoplasms, Connective and Soft Tissue / genetics
  • Neoplasms, Connective and Soft Tissue / secondary
  • Phenotype
  • Proto-Oncogene Proteins c-kit / drug effects
  • Proto-Oncogene Proteins c-ret / drug effects
  • Pyrroles / therapeutic use*
  • RNA-Binding Protein EWS
  • RNA-Binding Proteins / genetics
  • Receptor, Platelet-Derived Growth Factor beta / drug effects
  • Receptors, Steroid / genetics
  • Receptors, Thyroid Hormone / genetics
  • Sunitinib
  • TATA-Binding Protein Associated Factors / genetics
  • Treatment Outcome
  • Vascular Endothelial Growth Factor Receptor-2 / drug effects
  • fms-Like Tyrosine Kinase 3 / drug effects


  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Calmodulin-Binding Proteins
  • DNA-Binding Proteins
  • EWSR1 protein, human
  • Indoles
  • NR4A3 protein, human
  • Pyrroles
  • RNA-Binding Protein EWS
  • RNA-Binding Proteins
  • Receptors, Steroid
  • Receptors, Thyroid Hormone
  • TAF15 protein, human
  • TATA-Binding Protein Associated Factors
  • FLT3 protein, human
  • KDR protein, human
  • Proto-Oncogene Proteins c-kit
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • Receptor, Platelet-Derived Growth Factor beta
  • Vascular Endothelial Growth Factor Receptor-2
  • fms-Like Tyrosine Kinase 3
  • Sunitinib

Supplementary concepts

  • Chondrosarcoma, Extraskeletal Myxoid