Dermatofibrosarcoma protuberans-derived fibrosarcoma: Response to escalated-dose imatinib mesylate (IM) and second-generation kinase inhibitor nilotinib.

Abstract

e20529 Background: Dermatofibrosarcoma protuberans (DFSP) is a dermal sarcoma typically carrying a translocation between chromosomes 17 and 22 that generates functional platelet-derived growth factor B (PDGFB). Imatinib is active in locally advanced and metastatic DFSP harboring t(17;22) with objective response rates of 50% in pooled clinical trial results. Less is known of imatinib, or second generation kinase inhibitor nilotinib, efficacy in fibrosarcomatous-DFSP having the PDGF rearrangement. Methods: From January 2007, 2 patients with locally advanced high grade Fibrosarcoma (FS) arising in DFSP were treated with 400 mg IM. We also identified 4 DFSP and 2 FS patients without DFSP from 2003. Results: Both patients were male age 60/51 with ECOG PS=0. Patient A weighed 142 kg and had a subjective response, RECIST SD and continued PET scan activity. Dose was eventually escalated to 1600 mg. Imatinib trough level = 3710 ng/ml. The shoulder mass was resected with 1mm margin at 29 months. 54% of the cells contained PDGFB rearrangement by FISH. The patient died at 32 months of brain metastsasis. Patient B had RECIST SD and continued PET activity after 4 months of treatment and had 1 month of IM escalation to 800mg. He underwent resection of his abdominal mass but relapsed in the inguinal node and lungs. After three cycles of MAID and two cycles of gemcitabine/docetaxel he was treated with compassionate use nilotinib (Tasigna). He died of disease progression 4 weeks after initiation of nilotinib (OS from presentation 20 months). 49% of the cells contained PDGFB rearrangement at presentation and 63% at resection. Conclusions: resistance to imatinib was not related to PDGFRB expression and was not overcome by dose escalation of imatinib or nilotinib.