Imatinib DFSP

Background

Pooled analysis of two independent Phase 2 trials of imatinib in advanced dermatofibrosarcoma protuberans (DFSP). DFSP nearly always harbors t(17;22) generating COL1A1-PDGFB fusion, a direct target of imatinib (PDGFR inhibitor). EORTC trial (N=16): 14-wk PFS rate primary endpoint; PDGFB confirmation required. SWOG trial (N=8): confirmed ORR primary endpoint; t(17;22) confirmed post-enrollment. Total N=24; 7 with metastases.

Interventions and follow up

Treatment: Imatinib 400 mg orally twice daily (some protocols 400 mg daily) until progression or intolerance (single-arm)
Primary endpoint: Objective response rate (RECIST/WHO criteria)
mFollow up: Not formally reported; 1-year OS data available

Results

ORR (partial response): 46% (11/24)
Stable disease: 29% (7/24)
Progressive disease: 17% (4/24)
Median TTP: 1.7 years
1-year OS: 87.5%

Adverse events

Tolerability: well tolerated at 400 mg/day
Most common (grade 1–2): edema, nausea, fatigue, myalgia
Grade ≥3: uncommon
Discontinuation: 1 for toxicity; 2 after complete surgical resection

Conclusions

Imatinib achieved 46% ORR and median TTP 1.7 years in t(17;22)-positive advanced DFSP with favorable tolerability. Responses in both classic and fibrosarcomatous subtypes; no difference between 400 mg/day and 800 mg/day. Supported FDA approval for unresectable/locally advanced or metastatic DFSP.

Key Limitations

Pooled, single-arm, very small N (24); rare disease. No comparator; ORR surrogate endpoint. Median follow-up not reported; heterogeneous dosing protocols.

Clinical Context

Imatinib FDA-approved for unresectable/recurrent/metastatic DFSP; ESMO-endorsed systemic option for advanced disease and in the neoadjuvant setting to enable resection. Surgery remains primary treatment for resectable DFSP.

References