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Molecular and Clinical Analysis of Locally Advanced Dermatofibrosarcoma Protuberans Treated With Imatinib: Imatinib Target Exploration Consortium Study B2225

From the Peter MacCallum Cancer Centre, East Melbourne, Australia; Dana-Farber Cancer Institute and Harvard Medical School, Sarcoma Center; Department of Pathology, Brigham & Women's Hospital, Boston, MA; Universiteit Ziekenhuis Gasthuisberg dienst oncology; Cytogenetics and Molecular Genetics of Human Malignancies, Department of Human Genetics, Catholic University of Leuven, Leuven, Belgium; Departments of Medicine and Pathology, Oregon Health Sciences University Cancer Institute and Portland Veterans Affairs Medical Center, Portland, OR; and Clinical Research Oncology, Novartis Pharma AG, Basel, Switzerland

Address reprint requests to information: Grant McArthur, MB, BS, PhD, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Australia 3002; e-mail: grant.mcarthur{at}petermac.org

PURPOSE: The cutaneous malignant tumor dermatofibrosarcoma protuberans (DFSP) is typically associated with a translocation between chromosomes 17 and 22 that places the platelet-derived growth factor–B (PDGFB) under the control of the collagen 1A1 promoter. The purpose of this study was to evaluate molecular, cytogenetic, and kinase activation profiles in a series of DFSPs and to determine whether these biologic parameters are correlated with the clinical responses of DFSP to imatinib.

PATIENTS AND METHODS: We analyzed the objective radiologic and clinical response to imatinib at 400 mg twice daily in eight patients with locally advanced DFSP and two patients with metastatic disease.

RESULTS: Each of eight patients with locally advanced DFSP had evidence of t(17;22) and showed a clinical response to imatinib. Four of these patients had complete clinical responses. The two patients with metastatic disease had fibrosarcomatous histology and karyotypes that were substantially more complex than those typically associated with localized DFSP. One patient with metastatic DFSP and an associated t(17;22) had a partial response to imatinib but experienced disease progression after 7 months of therapy. In contrast, the other patient with metastatic disease had a tumor lacking t(17;22), and there was no clinical response to imatinib. Unexpectedly, there was minimal platelet-derived growth factor receptor–beta phosphorylation in the untreated DFSP, despite the documented presence of a PDGFB autocrine mechanism.

CONCLUSION: Imatinib has clinical activity against both localized and metastatic DFSP with t(17;22). However, fibrosarcomatous variants of DFSP lacking t(17;22) may not respond to imatinib.

Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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