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Clinical Trial
. 2023 Jan;12(2):1532-1539.
doi: 10.1002/cam4.5044. Epub 2022 Aug 10.

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

Steven Attia  1 , Vanessa Bolejack  2 , Kristen N Ganjoo  3 , Suzanne George  4 , Mark Agulnik  5 , Daniel Rushing  6 , Elizabeth T Loggers  7 , Michael B Livingston  8 , Jennifer Wright  9   10 , Sant P Chawla  11 , Scott H Okuno  12 , Denise K Reinke  13 , Richard F Riedel  14 , Lara E Davis  15 , Christopher W Ryan  15 , Robert G Maki  16
Affiliations
Clinical Trial

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

Steven Attia et al. Cancer Med. 2023 Jan.

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.

Keywords: (5): CIC-DUX4; Ewing sarcoma; clinical trial; regorafenib.

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Conflict of interest statement

The following conflicts of interest are reported. SA: Research Funding: AB Science, Bayer, Blueprint Medicines, CBA Pharmaceuticals, CytRx, Daichi Sankyo, Deciphera, Desmoid Tumor Research Foundation, Epizyme, Genmab, Gradilis, Immune Design, Incyte, Karyopharm Pharmaceuticals, Lilly, Merck, Morphotek, Novartis, Pilogen, Takeda Oncology, Threshold Pharmaceuticals, Tracon. SG: Research Funding: Bayer, Blueprint Genetics, Deciphera, Novartis, Pfizer. Advisory Board: AstraZeneca. Other Interests: Abbvie. DRei: Research funding: Bayer. DRus: Advisory Board: Lilly. SC: Research funding: Amgen, CytRx Corporation, GlaxoSmithKline, Ignyta, Immune Design, Roche, Threshold Pharamceuticals, Tracon. RR: Research Funding: AADi, AROG, Ignyta, Immune Design, Karyopharm, Lilly, Limbguard LLC, NanoCarrier, Novartis, Oncternal, Plexxikon, Threshold, Tracon. Advisory Board: Bayer, EISAI, EMD Serono, Janssen, Loxo. CR: Research funding: Argos Therapeutics, Bayer, BMS, CytRx, Daiichi Sankyo, Eisai, Exelixis, Genentech, GlaxoSmithKline, Novartis, Janssen, Karyopharm Therapeutics, MabVax, Merck, Morphotek, Threshold Pharmaceuticals, Tracon. RM: Research funding: Astex, Bayer, Boeringer Ingleheim, Exelixis, Genentech, Karyopharm, Presage, Rain, Springworks, Synox, Tracon. Consulting/Honoraria: AADi, Bayer, Deciphera, Immune Design, Karyopharm, Presage, Springworks, American Board of Internal Medicine, American Society for Clinical Oncology, UptoDate. Other: Bayer, Tracon. VB, KG, EL, ML, JW, SO, LD: No conflicts to report.

Figures

FIGURE 1
FIGURE 1
Progression‐free survival by Kaplan–Meier method.
FIGURE 2
FIGURE 2
Overall survival by Kaplan–Meier method.
FIGURE 3
FIGURE 3
Swimmer's plot of the duration of treatment with regorafenib for the Ewing family sarcoma patients treated on SARC024.
See this image and copyright information in PMC

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References

    1. Brennan MF, Antonescu C, Maki RG. Sarcomas more common in children. Management of Soft Tissue Sarcoma. Springer; 2013. ISBN 978‐1‐4614‐5003‐0: 2210‐250.
    1. Casey DA, Wexler LH, Merchant MS, et al. Irinotecan and temozolomide for Ewing sarcoma: the memorial Sloan‐Kettering experience. Pediatr Blood Cancer. 2009;53(6):1029‐1034. - PubMed
    1. Wagner LM, McAllister N, Goldsby RE, et al. Temozolomide and intravenous irinotecan for treatment of advanced Ewing sarcoma. Pediatr Blood Cancer. 2007;48(2):132‐139. - PubMed
    1. Farhat R, Raad R, Khoury NJ, et al. Cyclophosphamide and topotecan as first‐line salvage therapy in patients with relapsed Ewing sarcoma at a single institution. J Pediatr Hematol Oncol. 2013;35(5):356‐360. - PubMed
    1. Hunold A, Weddeling N, Paulussen M, Ranft A, Liebscher C, Jürgens H. Topotecan and cyclophosphamide in patients with refractory or relapsed Ewing tumors. Pediatr Blood Cancer. 2006;47(6):795‐800. - PubMed

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