A phase II trial of regorafenib in patients with advanced Ewing sarcoma and related tumors of soft tissue and bone: SARC024 trial results.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Attia, S; Bolejack, V; Ganjoo, KN; George, S; Agulnik, M; Rushing, D; Loggers, ET; Livingston, MB; Wright, J; Chawla, SP; Okuno, SH; Reinke, DK; Riedel, RF; Davis, LE; Ryan, CW; Maki, RG

Published Date

  • January 2023

Published In

Volume / Issue

  • 12 / 2

Start / End Page

  • 1532 - 1539

PubMed ID

  • 35950293

Pubmed Central ID

  • PMC9883574

Electronic International Standard Serial Number (EISSN)

  • 2045-7634

Digital Object Identifier (DOI)

  • 10.1002/cam4.5044


  • eng

Conference Location

  • United States