The treatment of TGCT can be challenging and may include the use of medications. Sometimes tumors cannot be entirely removed using surgery or the risk of complications from surgery outweighs the possible benefit. Other times tumors recur and are not amenable to surgery. A mix of anti-inflammatories, steroids, and pain medication can be given to manage the symptoms of TGCT, however, these do not treat the disease itself. In cases of either inoperable or recurrent TGCT, a medical oncologist can be a vital part of a healthcare team.
Surgery is often curative for localized TGCT due to the tumor, typically, having a defined boundary. This clear boundary allows the tumor to be completely removed during surgery (1). However, complete removal is not always possible. In diffuse TGCT, complete removal using surgery is less likely due to the size of the tumor, the possibility of multiple loose bodies, and a lack of clear boundary. In some cases of diffuse TGCT, following multiple surgeries, the tumors can recur again and again. Repeated surgery can lead to osteoarthritis and other morbidities. Therefore, pharmaceutical options are available to treat patients with diffuse or recurrent TGCT.
CSF-1 INHIBITORS
CSF1 inhibitors are types of drugs that fall into a drug class called the tyrosine kinase inhibitors. Genes dictate what proteins are made, like a genetic blueprint. The gene that makes the protein, CSF1, is located within a family, called the tyrosine kinase family. Like a family tree, other members of the tyrosine kinase family make proteins that look and act similar to each other. Members of this family function similarly and their protein can be targeted in a similar way. Other tyrosine kinase inhibitors include nilotinib (Tasigna) and imatinib (Gleevec), which are used off-label for diffuse TGCT (2,3,4). TGCT uses the CSF1 protein to recruit other cells to become part of the tumor. Since CSF1 is part of the same family as other tyrosine kinases, it can be targeted with drugs already on market for other tyrosine kinase family members, like nilotinib and imatinib. These drugs act by disrupting the signaling between tumor cells and surrounding cells in the joint, halting tumor growth. Go to About TGCT to learn more about the biology of TGCT. Currently, there is a single drug approved in August 2019 for the treatment of recurrent and inoperable TGCT. Instead of targeting other members of the tyrosine kinase family to assert its anti-tumor activity, it directly targets CSF1. Pexidartinib (TURALIO™, Daiichi Sankyo) is the first FDA-approved treatment for adults with symptomatic TGCT that is not amenable to improvement from surgery (5). Pexidartinib works by inhibiting CSF1 from signaling to the TGCT and the surrounding cells. This disrupts the ability for the TGCT to recruit more cells, halting the growth.
For more information on on-going trials, go to Clinical Trials.
References
1. Nagase M, Araki A, Ishikawa N, et al. Tenosynovial Giant Cell Tumor, Localized Type With Extensive Chondroid Metaplasia: A Case Report With Immunohistochemical and Molecular Genetic Analysis. Int J Surg Pathol. 2020. doi:10.1177/1066896919889672 2. F.G.M. V, M.J.L. M, G. H, et al. Long-term efficacy of imatinib mesylate in patients with advanced Tenosynovial Giant Cell Tumor. Sci Rep. 2019. 3. Weaver C. Tenosynovial Giant Cell Tumor Treatment. Cancer Connect. https://news.cancerconnect.com/bone-cancer/tenosynovial-giant-cell-tumor-treatment-u1jsmV2RVUC1l6LHWX80Rg. Published 2019. 4. Gelderblom H, Pérol D, Chevreau C, et al. An open-label international multicentric phase II study of nilotinib in progressive pigmented villo-nodular synovitis (PVNS) not amenable to a conservative surgical treatment. J Clin Oncol. 2013. doi:10.1200/jco.2013.31.15_suppl.10516 5. FDA approves pexidartinib for tenosynovial giant cell tumor. Case Med Res. 2019. doi:10.31525/cmr-19c99e2
