Pexidartinib for the treatment of adult symptomatic patients with tenosynovial giant cell tumors.

Introduction Tenosynovial giant cell tumor (TGCT) is a benign mesenchymal tumor arising from the synovium of tendon sheats and joints, driven by colony-stimulating factor 1 (CSF1) over-expression. Standard treatment is surgery, but local recurrences are frequent, especially in diffuse TGCT subtype, rarely cured with surgery. When TGCT becomes a chronic condition, which may severely compromise joint function and quality of life, patients may need a systemic therapy. Areas covered: We reviewed the drugs on clinical development in TGCT, focusing on the pharmacodynamics, pharmacokinetics, efficacy, and toxicity profile of pexidartinib, the first drug approved in the US for TGCT, and on the open questions about its optimal use in clinical practice. Expert opinion CSFR1 inhibitors have opened a new avenue for treatment of TGCT patients. Pexidartinib is the first-in-class FDA approved agent for symptomatic locally advanced TGCT, based on a phase III study where pexidartinib showed high anti-tumor activity, improved patient symptoms, and functional outcome. A few cases of potentially life-threatening hepatic toxicity were observed. TGCT patients candidate to pexidartinib need to be carefully selected by the multidisciplinary board of center of expertise, balancing the expected risk-benefit ratio. Close monitoring of liver function and adequate education on the approved indication is warranted.