Pexidartinib Long-Term Hepatic Safety Profile in Patients with Tenosynovial Giant Cell Tumors

作者：James H. Lewis, Hans Gelderblom, Michiel A. J. van de Sande, Silvia Stacchiotti, John H. Healey, William D. Tap, Andrew J. Wagner, Antonio López–Pousa, Mihaela Druta, Chia‐Chi Lin, Hideo A. Baba, Youngsook Choi, Qiang Wang, Dale E. Shuster, Sebastian Bauer · 发表于：The Oncologist · 年份：2020 · DOI：10.1002/onco.13629 · 被引用次数：63 · 研究领域：Musculoskeletal synovial abnormalities and treatments、Tendon Structure and Treatment、Bone Tumor Diagnosis and Treatments

BACKGROUND: Pexidartinib is approved in the U.S. for tenosynovial giant cell tumors (TGCTs). Herein, we assessed the hepatic safety profile of pexidartinib across patients with TGCTs receiving pexidartinib. MATERIALS, AND METHODS: Hepatic adverse reactions (ARs) were assessed by type and magnitude of liver test abnormalities, classified as (a) isolated aminotransferase elevations (alanine [ALT] or aspartate [AST], without significant alkaline phosphatase [ALP] or bilirubin elevations), or (b) mixed or cholestatic hepatotoxicity (increase in ALP with or without ALT/AST and bilirubin elevations, based on adjudication). Median follow-up from initial pexidartinib treatment was 39 months (range, 32-82) in 140 patients with TGCTs across clinical studies NCT01004861, NCT02371369, NCT02734433, and NCT03291288. RESULTS: In total, 95% of patients with TGCTs (133/140) treated with pexidartinib (median duration of exposure, 19 months [range, 1-76]), experienced a hepatic AR. A total of 128 patients (91%) had reversible, low-grade dose-dependent isolated AST/ALT elevations without significant ALP elevations. Five patients (4%) experienced serious mixed or cholestatic injury. No case met Hy's law criteria. Onset of hepatic ARs was predominantly in the first 2 months. All five serious hepatic AR cases recovered 1-7 months following pexidartinib discontinuation. Five patients from the non-TGCT population (N = 658) experienced serious hepatic ARs, two irreversible cases. CONCLUSION: This pool...