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Regorafenib for the Treatment of Sarcoma

  • Sarcoma (SH Okuno, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Sarcomas are a rare group of tumors with many subtypes, conventionally classified into soft-tissue sarcomas and bone sarcomas. Chemotherapeutic regimens form the mainstay of systemic therapy but are not well defined beyond the first-line setting and clinical outcomes are variable. Tyrosine kinase inhibitors (TKIs), with a broad inhibition profile which have been shown to target tumor angiogenesis, have an established role in the treatment of sarcomas without characteristic driver alterations. One such TKI, regorafenib, has been evaluated in sarcomas and clinical data are discussed in this review. An overview of regorafenib data from five phase 2 and one phase 1b clinical trials in over 10 sarcoma subtypes (both soft-tissue and bone) in adult and pediatric patients is reviewed. Regorafenib demonstrated clinical benefit in patients with non-adipocytic soft-tissue sarcomas, osteosarcoma and Ewing sarcoma who had progressed on prior therapy. Patients with otherwise limited treatment options may therefore benefit from regorafenib therapy.

Plain language summary

Sarcomas are a type of cancer that start from the bones or soft tissues (such as muscle, blood vessel, or fat tissue) anywhere in the body. Sarcomas are rare – only about 1% of all cancers are sarcomas, and there are many different types. Sarcomas occur more often in children than in adults. People with sarcomas which cannot be removed by surgery are usually treated with chemotherapy first, but chemotherapy may only help some people and can cause a lot of side effects. Only a few chemotherapies work in sarcomas, and if they do not work or stop working the patient does not have many other treatment options. A different type of therapy known as "tyrosine kinase inhibitors" may work in these patients. These medicines, usually swallowed as a pill, target the way that sarcoma cells grow and may help patients in whom chemotherapy has not worked. Medical doctors and scientists tested "regorafenib", a type of tyrosine kinase inhibitor, in clinical trials. This publication summarizes the results from six clinical trials that tested regorafenib in over 500 adults, teenagers, and children with sarcomas. People included in these trials had more than ten different types of sarcomas in total, and usually had already received a treatment that had not stopped the sarcoma from growing. Regorafenib treatment helped people with certain types of sarcomas that developed from bones or soft tissues, but not fat tissue. Doctors also managed the side effects of regorafenib well for patients in these trials.

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Authors and Affiliations

  1. Department of Medicine, Léon Bérard Center, Lyon, France

    Jean-Yves Blay MD, PhD

  2. Medical Oncology Unit, La Timone University Hospital, Marseille, France

    Florence Duffaud MD, PhD

  3. Aix Marseille University (AMU), Marseille, France

    Florence Duffaud MD, PhD

  4. Dana-Farber Cancer Institute, Harvard Medical School, Cambridge, MA, USA

    Suzanne George MD

  5. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Robert G. Maki MD, PhD

  6. Medical Oncology Department, Oscar Lambret Cancer Center and Lille University, Lille, France

    Nicolas Penel MD, PhD

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  1. Jean-Yves Blay MD, PhD
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  2. Florence Duffaud MD, PhD
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  3. Suzanne George MD
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  4. Robert G. Maki MD, PhD
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  5. Nicolas Penel MD, PhD
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All authors contributed equally to the development of this review.

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Correspondence to Jean-Yves Blay MD, PhD.

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Acknowledgments

Medical writing and editorial support were provided by Emily Clark of OPEN Health Communications, London, UK, with financial support from Bayer.

Conflict of Interest

Jean-Yves Blay has received advisory/consultancy fees from Bayer, Roche, Deciphera, Bristol-Myers Squibbs, Merck Sharpe & Dohme, and Pharmamar. Jean-Yves Blay has received speaker honoraria from Bayer, Roche, Pharmamar, and Deciphera. Jean-Yves Blay has received research grants or funding from Bayer, Roche, Deciphera, Bristol-Myers Squibbs, Merck Sharpe & Dohme, Pharmamar, Novartis, and GlaxoSmithKline. Florence Duffaud has received advisory/consultancy fees from Bayer, Pharmamar, GlaxoSmithKline, and Deciphera. Florence Duffaud has given a sponsored lecture and received speaker honoraria from Pharmamar and has received research grants or funding from Bayer. Suzanne George owns stock in Abbott Laboratories. Suzanne George has received speaker honoraria from C-Stone. Suzanne George has received advisory/consultancy fees from Blueprint Medicines, Deciphera, Bayer, Lilly, UpToDate, Research to Practise, MORE Health, Daiichi, Kayothera, and Immunicum. Suzanne George has received research grants or funding from Blueprint Medicines, Deciphera, Daiichi Sankyo RD Novare, Merck, Eisai, Springworks Therapeutics, TRACON Pharma, and Theseus Pharmaceuticals. Suzanne George holds patents, royalties, or other intellectual property with UptoDate. Suzanne George has given expert testimony for Bayer. Robert G. Maki has received speaker honoraria or advisory/consultancy fees from AADi, Bayer, BioAlta, Decipehra, Immune Design, Karyopharm, Presage, Springworks, American Board of Internal Medicine, American Society for Clinical Oncology, and UptoDate. Robert G. Maki has received research grants or funding from Amgen, Astex, Bayer, BioAlta, Boeringer Ingleheim, Exelixis, Genentech, Karyopharm, Presage, Rain, Springworks, Synox, and TRACON Pharma. Robert G. Maki has received travel expenses from Bayer and Tracon. Nicolas Penel has received research grants or funding from Bayer.

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Blay, JY., Duffaud, F., George, S. et al. Regorafenib for the Treatment of Sarcoma. Curr. Treat. Options in Oncol. 23, 1477–1502 (2022). https://doi.org/10.1007/s11864-022-00990-0

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