IMATINIB FOR DERMATOFIBROSARCOMA PROTUBERANS

Clin Cancer Res. 2015 Aug 10. pii: clincanres.1243.2015. [Epub ahead of print]

Efficacy and biological activity of imatinib in metastatic dermatifibrosarcoma protuberans (DFSP).

Stacchiotti S1, Pantaleo MA2, Negri T3, Astolfi A4, Tazzari M5, Dagrada GP6, Urbini M7, Indio V8, Maestro R9, Gronchi A10, Fiore M11, Dei Tos AP12, Conca E13, Palassini E14, Vincenzi B15, Grosso F16, Pilotti S17, Castelli C18, Casali PG19.

Author information

Abstract

PURPOSE: 

To report on imatinib mesylate (IM) in patients with metastatic dermatofibrosarcoma protuberans (DFSP)/ fibrosarcomatous (FS)-DFSP and on the impact of the treatment on tumor biology Experimental Design:Ten consecutive patients treated with IM from 2007 to 2015 for a metastatic relapse from DFSP/FS-DFSP were identified. FISH analysis for COL1A1-PDGFb was performed. Two IM-treated and 4 naïve FS-DFSP were transcriptionally profiled by RNAseq on HiScanSQ platform. Differential gene expression was analyzed with edgeR (Bioconductor), followed by hierarchical clustering and Principal Component Analysis (PCA).

RESULTS: 

All cases featured fibrosarcomatous in the metastasis and retained the COL1A1-PDGFB. Best RECIST response was: 8 PR, 1 SD, 1 PD. Median PFS was 11 months. Five patients received surgery after IM and all relapsed. IM was restored in 4 patients with a new response. After IM, the most up-regulated genes included those encoding for immunoglobulins and those affecting functions and differentiation of endothelial cells. Pathway enrichment analysis revealed up-regulation in genes involved in antigen processing and presentation, NK mediated cytotoxicity, and drug and xenobiotics metabolism. Conversely, a significant down-regulation of kinase signaling pathways was detected.

CONCLUSIONS: 

All metastatic cases were fibrosarcomatous. Most patients responded to IM but PFS was shorter than reported in published series which included both DFSP and FS/DFSP. All patients operated after IM had a relapse, suggesting that IM cannot eradicate metastatic cases and that the role of surgery is limited. Transcriptional profile of naïve and post-treatment samples pointed the contribution of immune infiltrates in sustaining the response to IM.