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

Autor: Attia S; Mayo Clinic Jacksonville, Jacksonville, Florida, USA., Bolejack V; Cancer Research and Biostatistics, Seattle, Washington, USA., Ganjoo KN; Stanford Cancer Institute, Stanford, California, USA., George S; Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston, Massachusetts, USA., Agulnik M; City of Hope, Duarte, California, USA., Rushing D; Indiana University, Bloomington, Indiana, USA., Loggers ET; Fred Hutchinson Cancer Research Center, Seattle, Washington, USA., Livingston MB; Levine Cancer Institute, Charlotte, North Carolina, USA., Wright J; Huntsman Cancer Institute, Salt Lake City, Utah, USA.; Lilly Pharmaceuticals, Indianapolis, Indiana, USA., Chawla SP; Sarcoma Oncology Center, Santa Monica, California, USA., Okuno SH; Mayo Clinic, Rochester, Minnesota, USA., Reinke DK; Sarcoma Alliance for Research through Collaboration, Ann Arbor, Michigan, USA., Riedel RF; Duke Cancer Institute, Durham, North Carolina, USA., Davis LE; Oregon Health & Science University, Portland, Oregon, USA., Ryan CW; Oregon Health & Science University, Portland, Oregon, USA., Maki RG; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jazyk: angličtina
Zdroj: Cancer medicine [Cancer Med] 2023 Jan; Vol. 12 (2), pp. 1532-1539. Date of Electronic Publication: 2022 Aug 10.
DOI: 10.1002/cam4.5044
Abstrakt: 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.
(© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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