Pexidartinib Long-Term Hepatic Safety Profile in Patients with Tenosynovial Giant Cell Tumors
Lewis, James H. (MedStar Georgetown University Hospital)
Gelderblom, Hans J (Leiden University Medical Center)
van de Sande, Michiel (Leiden University Medical Center (Països Baixos))
Stacchiotti, Silvia (Fondazione IRCCS Istituto Nazionale dei Tumori (Milà, Itàlia))
Healey, John H. (Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College (Nova York, Estats Units d'Amèrica))
Tap, William D. (Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College (Nova York, Estats Units d'Amèrica))
Wagner, Andrew J. (Dana-Farber Cancer Institute (Boston, Estats Units d'Amèrica))
López Pousa, Antonio (Institut d'Investigació Biomèdica Sant Pau)
Druta, Mihaela (Moffitt Cancer Center (Tampa, Florida))
Lin, ChiaChi Chi Josh (National Taiwan University Hospital (Taipei, Taiwan))
Baba, Hideo Andreas (University Hospital Essen (Alemanya))
Choi, Youngsook (Daiichi Sankyo. Inc (Nova Jersey, Estats Units))
Wang, Qiang (Daiichi Sankyo. Inc (Estats Units))
Shuster, Dale E. (Daiichi Sankyo. Inc (Estats Units)))
Bauer, Sebastian (University of Duisburg-Essen (Alemanya))

Data:	2021
Resum:	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 pooled analysis provides information to help form the basis for the treating physician's risk assessment for patients with TCGTs, a locally aggressive but typically nonmetastatic tumor. In particular, long-term treatment with pexidartinib has a predictable effect on hepatic aminotransferases and unpredictable risk of serious cholestatic or mixed liver injury. Implications for Practice: This is the first long-term pooled analysis to report on the long-term hepatic safety of pexidartinib in patients with tenosynovial giant cell tumors associated with severe morbidity or functional limitations and not amenable to improvement with surgery. These findings extend beyond what has been previously published, describing the observed instances of hepatic toxicity following pexidartinib treatment across the clinical development program. This information is highly relevant for medical oncologists and orthopedic oncologists and provides guidance for its proper use for appropriate patients within the Pexidartinib Risk Evaluation and Mitigation Safety program.
Nota:	Altres ajuts: National Institutes of Health/National Cancer Institute (P30 CA008748); Daiichi Sankyo, Co., Ltd.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	The Oncologist, Vol. 26 Núm. 5 (may 2021) , p. e863-e873, ISSN 1549-490X

DOI: 10.1002/onco.13629
PMID: 33289960

11 p, 900.3 KB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Recerca Sant Pau
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