Abstract
Background: Regorafenib is one of several FDA-approved cancer therapies targeting multiple tyrosine kinases. However, there are few subtype-specific data regarding kinase inhibitor activity in sarcomas. We report results of a single arm, phase II trial of regorafenib in advanced Ewing family sarcomas. Methods: Patients with metastatic Ewing family sarcomas (age ≥ 18, ECOG 0–2, good organ function) who had received at least one line of therapy and experienced progression within 6 months of registration were eligible. Prior kinase inhibitors were not allowed. The initial dose of regorafenib was 160 mg oral days 1–21 of a 28-day cycle. The primary endpoint was estimating progression-free rate (PFR) at 8 weeks employing RECIST 1.1. Results: Thirty patients (median age, 32 years; 33% women [10 patients]; bone primary, 40%; extraskeletal primary, 60%) enrolled at 14 sites. The most common grade 3 or higher toxicities were hypophosphatemia (5 grade 3, 1 grade 4), hypertension (2 grade 3), elevated ALT (2 grade 3). Sixteen patients required dose reductions, most often for hypophosphatemia (n = 7 reductions in 6 patients); two stopped regorafenib for toxicity. There was one death unrelated to treatment in the 30-day post-study period. Median progression-free survival (PFS) was 14.8 weeks (95% CI 7.3–15.9); PFR at 8 weeks by Kaplan–Meier analysis was 63% (95% CI 46–81%). The RECIST 1.1 response rate was 10%. Median OS was 53 weeks (95% CI 37–106 weeks). Conclusions: Regorafenib has modest activity in the Ewing family sarcomas. Toxicity was similar to that seen in approval studies.
Original language | English (US) |
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Pages (from-to) | 1532-1539 |
Number of pages | 8 |
Journal | Cancer medicine |
Volume | 12 |
Issue number | 2 |
DOIs | |
State | Published - Jan 2023 |
Keywords
- (5): CIC-DUX4
- Ewing sarcoma
- clinical trial
- regorafenib
ASJC Scopus subject areas
- Oncology
- Radiology Nuclear Medicine and imaging
- Cancer Research