A phase II trial of imatinib (IM) in relapsed, nonresectable chondrosarcoma (CS) expressing platelet-derived growth factor receptor-α or -β (PDGFR-α/PDGFR-β): An Italian Sarcoma Group study.

Abstract

10060 Background: CS is a rare and heterogeneous disease in which, after failure of surgery and radiotherapy, chemotherapy has a marginal role, if any. Different molecular pathways were shown to be activated in CS. Particularly, both PDGFR isoforms may be expressed and phosphorylated (PC Hogendoorn, MS Lagonigro). Since IM was proven effective in other sarcomas sharing the activation of this pathway, we investigated the activity of IM in advanced CS in a phase II trial. Methods: Between January 2007 and June 2009, 26 subjects, median age 61 (23-81), affected by metastatic, not resectable CS were treated with 400 mg of IM b.i.d. until progression or unacceptable toxicity. Eligibility criteria were: ≥1 prior line of chemotherapy, and immunohistochemical expression of either PDGFR-α or PDGFR-β . Primary objective was the percentage of patients free from progression at 4-month (Kaplan and Meier). Secondary objectives were: objective response (RECIST), overall survival, toxicity, clinical benefit (Pain Analgesic Score). Results: In all patients PDGFR was phosphorylated. Planned IM dose was delivered, but 60% (15) needed dose reductions due to manageable and short lasting toxicity [Median administered dose was 83% (74-91%) of full expected-one]. PFS at 4-month was 31% (2.6-7.8 months) (8). Median overall survival was 10.9 months. No objective responses, long lasting freedom from progression or improvement in PAS were observed. Conclusions: Imatinib, as expected, was relatively well tolerated, but it failed to show a meaningful clinical activity in term of both freedom from progression and tumor shrinkage. Advanced CS remains a disease not curable, and effective targeted therapies are still awaited. No significant financial relationships to disclose.