Tenosynovial Giant Cell Tumor Treatment

by Dr. C.H. Weaver M.D. 12/2019

Tenosynovial Giant Cell Tumor of bone (TGCT) is a rare, aggressive, benign osteolytic tumor in which bone destruction is mediated by a protein known as the RANK ligand. This protein regulates the activity of osteoclasts (cells that break down bone). GCTB typically affects younger adults between the ages of 20 to 40.

Historically, the only treatment option for patients with GCTB was surgery; however, patients who undergo surgery often have recurrent disease or devastating consequences, such as amputation and about 25 to 30 percent of patients with GCTB have to undergo joint replacements. The RANK ligand inhibitor was approved for the treatment of TGCT and recent research has expanded the treatment options. Inhibition of the CSF1/CSF-1 receptor (CSF-1R) signaling appears effective in the treatment of locally advanced and recurrent diffuse TGCT.

Gleevec (Imatinib mesylate) is a CSF-1R kinase inhibitor and researcher collected and analyzed data from 62 patients with locally advanced, recurrent, or metastatic TGCT from 12 cancer centers that used imatinib mesylate 400 mg to 600mg for treatment of TGCT.

Overall a total of 17 patients achieved a complete or partial response to Imatinib mesylate treatment and 71% and 48% of patients survived without cancer progression at 1 and 5 years, respectively from initiation of treatment.

It is hoped that the more potent CSF-1R inhibitors currently in development which include emactuzumab, pexidartinib and cabiralizumab will be more effective when used alone or in combination with Imatinib mesylate.

Turalio (pexidartinib)The phase 3 ENLIVEN clinical trial was designed to evaluate pexidartinib in TGCT patients not amenable to surgical resection. Overall 120 patients with TGCT were enrolled in the phase clinical study and treated with either pexidartinib no additional therapy and directly compared. Treatment with pexidartinib consisted of 1000 mg pexidartinib daily for the first 2 weeks, followed by 800 mg daily for 22 weeks.

Overall 24 (39%) of patients treated with pexidartinib responded to treatment, and 13% experienced serious side effects. The most common pexidartinib caused side effects were changes in hair color (67%), fatigue (54%), and nausea (38%).

Both Turalio and Gleevec represent potential new treatment options for TGCT and continued evaluation of these precision medicines is ongoing to determine their optimal use.

References:

  1. Sci Rep. 2019 Oct 10.
  1. Lancet. 2019 Aug 10. Epub 2019 Jun 19
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