A multicenter phase II study of pazopanib in patients with unresectable dermatofibrosarcoma protuberans.
Fiche publication
Date publication
septembre 2020
Journal
The Journal of investigative dermatology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DALAC Sophie
Tous les auteurs :
Delyon J, Porcher R, Battistella M, Meyer N, Adamski H, Bertucci F, Guillot B, Jouary T, Leccia MT, Dalac S, Mortier L, Ghrieb Z, Meda LD, Vicaut E, Pedeutour F, Mourah S, Lebbe C
Lien Pubmed
Résumé
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. 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), 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.
Mots clés
DFSP, dermatofibrosarcoma protuberans, pazopanib
Référence
J. Invest. Dermatol.. 2020 Sep 18;: