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 6months of registration were eligible. Prior kinase inhibitors were not allowed. The initial dose of regorafenib was 160mg oral days 1-21 of a 28-day cycle. The primary endpoint was estimating progression-free rate (PFR) at 8weeks employing RECIST 1.1.RESULTS: Thirty patients (median age, 32years; 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 14.8weeks (95% CI 7.3-15.9); PFR at 8weeks by Kaplan-Meier analysis was 63% (95% CI 46-81%). The RECIST 1.1 response rate was 10%. Median OS was 53weeks (95% CI 37-106weeks).CONCLUSIONS: Regorafenib has modest activity in the Ewing family sarcomas. Toxicity was similar to that seen in approval studies.

View details for DOI 10.1002/cam4.5044

View details for PubMedID 35950293