BioProject

Dermatofibrosarcoma protuberans (DFSP) is a soft-tissue sarcoma characterized by a high risk of local infiltration. More...

Dermatofibrosarcoma protuberans (DFSP) is a soft-tissue sarcoma characterized by a high risk of local infiltration. The identification of the COL1A1-PDGFB t(17;22) translocation activating the PDGF pathway led to the use of imatinib in unresectable DFSP, with a response rate of 36-80%. Pazopanib is a multitarget tyrosine kinase inhibitor approved for soft tissue sarcomas. We conducted a phase II study of patients with unresectable DFSP to evaluate the efficacy and safety of pazopanib. Patients received 800 mg pazopanib daily. The primary endpoint was the objective response rate defined as the reduction of the largest diameter of the tumor ≥30% at 6 months or at surgery assessed by physical examination. Twenty-three patients, including one pre-treated with imatinib, were enrolled. With a median follow-up of 6.2 months (interquartile range 5.6-7.8 months), 5 patients (22%, 95% CI: 7-22%) had a partial response to pazopanib. The best objective response rate was 30% (95% CI 13-53%) using RECIST. One patient with metastatic DFSP previously treated with imatinib died after 2.4 months. Nine (39%) patients discontinued the treatment due to adverse events. Pharmacodynamics analyses of tumor samples were conducted: the enrichment of EGF and the EGFR-associated gene panel was associated with resistance, suggesting that EGFR-targeted therapies could be a therapeutic option to explore in DFSP. Overall design: tumor samples were tested at baseline and during treatment with pazopanib for the mRNA expression of 302 genes involved in cell cycle, angiogenesis, apoptosis, proliferation (duplicate) Less...