Imatinib Mesylate in Advanced Dermatofibrosarcoma Protuberans: Pooled Analysis of Two Phase II Clinical Trials

Abstract

Purpose 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). Patients and Methods Two distinct phase II trials of imatinib (400 to 800 mg daily) in patients with locally advanced or metastatic DFSP were conducted and closed prematurely, one in Europe (European Organisation for Research and Treatment of Cancer [EORTC]) with 14-week progression-free rate as the primary end point and the other in North America (Southwest Oncology Group [SWOG]) with confirmed objective response rate as the primary end point. In the EORTC trial, confirmation of PDGFB rearrangement was required, and surgery was undertaken after 14 weeks if feasible. The SWOG study confirmed t(17;22) after enrollment. Results Sixteen and eight patients were enrolled onto the EORTC and SWOG trials, respectively. Tumor size ranged from 1.2 to 49 cm. DFSP was located on head/neck, trunk, and limb in seven, 11, and six patients, respectively, and was classic, pigmented, and fibrosarcomatous DFSP in 13, one, and nine patients, respectively. Metastases were present in seven patients (lung involvement was present six patients). Eleven patients (4%) had partial response as best response, and four patients had progressive disease as best response. Median time to progression (TTP) was 1.7 years. Imatinib was stopped in 11 patients because of progression, one patient because of toxicity, and two patients after complete resection of disease. Median overall survival (OS) time has not been reached; 1-year OS rate was 87.5%. Conclusion Imatinib is active in DFSP harboring t(17;22) including fibrosarcomatous DFSP, with objective response rate approaching 50%. Response rates and TTP did not differ between patients taking 400 mg daily versus 400 mg twice a day.

Trends in survival for patients with metastatic soft‐tissue sarcoma

“…10,11 In recent years, however, the insight has emerged that systemic therapy should become more tailored, and particularly for STS, according to histologic subtype. This approach is illustrated clearly by the relevant activity of imatinib in advanced dermatofibrosarcoma protuberans, 12,13 paclitaxel in angiosarcoma, 14,15 gemcitabine in leiomyosarcomas, 16,17 trabectedin in patients with myxoid/round cell liposarcomas, 18 and of mammalian target of rapamycin inhibitors in perivascular epithelioid cell tumors. 19 This evolution has been associated over the last 2 decades with the widespread use of additional lines of chemotherapy along with first-line anthracycline-based regimens; the increasing participation of patients with STS in investigational agents trials; the increased used of locoregional treatments for metastatic disease (surgery, radiofrequency ablation); and the general improvement in oncology supportive care.…”

Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial

“…[12][13][14] Despite the large number of genomic mutations in soft-tissue sarcomas no other targeted treatment is eff ective and the role of anti-angiogenic treatment is unclear. [15][16][17] Three phase 2 studies have been done to test antiangiogenic treatment.…”

Efficacy and Biological Activity of Imatinib in Metastatic Dermatofibrosarcoma Protuberans (DFSP)

“…In contrast, the role of IM in the metastatic setting is not clarified. Both the prospective and the retrospective studies reported so far analyzed locally advanced and metastatic patients together, and the efficacy of IM treatment was not investigated specifically in FS-DFSP (11)(12)(13)(14)(15). We already reported on 4 patients with advanced, translocated FS-DFSP (3 metastatic, one locally advanced) who received IM (5).…”