Imatinib Treatment for Locally Advanced or Metastatic Dermatofibrosarcoma Protuberans

Abstract

IMPORTANCE Dermatofibrosarcoma protuberans (DFSP) has the potential for local destruction and recurrence, although it carries a low risk of metastasis. Complete surgical resection with negative margins is considered the gold standard for treatment; however, there are cases that are unresectable owing to tumor extension or size or owing to risk of cosmetic and/or functional impairment. Imatinib treatment has been used for locally advanced or metastatic DFSP.OBJECTIVE To evaluate the usefulness of imatinib for treating DFSP. EVIDENCE REVIEWWe conducted a systematic review on the PubMed and Embase databases for articles published from September 2002 through October 2017 using the key words "dermatofibrosarcoma" or "dermatofibrosarcoma protuberans" AND "therapy" AND "imatinib." References within retrieved articles were also reviewed to identify additional studies. Studies of adults with histologically proven DFSP treated with imatinib as monotherapy or as an adjuvant or neoadjuvant therapy to surgery were included. Extracted data were analyzed using descriptive statistics. PRISMA guidelines were followed. All analysis took place October through December 2017.FINDINGS Nine studies met inclusion criteria; 152 patients were included. The calculated mean patient age was 49.3 years (range, 20-73 years). Calculated mean tumor diameter was 9.9 cm (range, 1.2-49.0 cm). When COL1A1-PDGFβ protein translocation (collagen, type 1, alpha 1-platelet-derived growth factor β) was reported, it was present in 90.9% of patients (111 of 122). Complete response was seen in 5.2% of patients (8 of 152), partial response in 55.2% (84 of 152), stable disease in 27.6% (42 of 152), and progression in 9.2% (14 of 152). Four of the 152 patients (2.6%) were excluded from the analysis owing to unknown or unevaluable response. There were no differences in response rate using 400-mg or 800-mg daily doses (67.5% or 27 of 40 patients for 400-mg dose vs 67.1% or 49 of 73 patients for 800-mg dose complete or partial response; P > .99). Adverse events were present in at least 73.5% of cases (78 of 106); severe adverse events were present in 15.1% of cases (20 of 132). CONCLUSIONS AND RELEVANCEImatinib is a useful directed therapy in patients with DFSP who are not surgical candidates owing to disease extension or significant cosmetic or functional impairment. There seems to be no difference between 400-or 800-mg daily doses.

Comparing the efficacy of cancer therapies between subgroups in basket trials

“…These malignancies were represented by 7 to 14 patients each, out of 186, confirming that statistically significant drug activity can be detected in small subgroups within a basket trial. Imatinib was approved for use in dermatofibrosarcoma protuberans by the FDA in 2006, and, following a phase 2 study published in 2010 (NCT00122473) it was incorporated into the National Comprehensive Cancer Network's treatment guidelines for this malignancy (Navarrete-Dechent et al, 2019). The use of imatinib in hypereosinophilic syndrome is supported by case studies (Gleich et al, 2002;Pardanani and Tefferi, 2004) and our analysis demonstrates additional support in a Phase II basket trial (Heinrich et al, 2008).…”

A Rare Malignant Disease, Dermatofibrosarcoma Protuberans of the Breast: A Retrospective Analysis and Review of Literature

“…It is reported that most DFSP have the translocation t(17; 22) (q22; q13), resulting in the COL1A1-PDGF β fusion gene, which provides a biological basis for treatment with tyrosine kinase inhibitors, such as imatinib [ 52 ]. In the advanced or metastatic group, imatinib therapy is warranted if a unique translocation is confirmed [ 53 , 54 ]. In a systematic review including 152 locally advanced or metastatic DFSP patients who received imatinib treatment, the results found that imatinib is a significantly effective therapy in these patients, with a complete response seen in 5.2% of patients and a partial response in 55.2% [ 53 ].…”

Dermatofibrosarcoma Protuberans Mimicking Primary Breast Neoplasm: A case report and literature review

“…16 Imatinib treatment has been also used for metastatic DFSP. 17 Long-term follow-up requires strict monitoring every 6-12 months with ultrasound and tissue biopsy in cases of suspected recurrence. The 10-year survival rate is >99%.…”