Ripretinib in gastrointestinal stromal tumor: the long-awaited step forward.

Autor:	Lostes-Bardaji MJ; Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain., García-Illescas D; Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain., Valverde C; Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain., Serrano C; Sarcoma Translational Research Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, P/Vall d'Hebron 119-129, Barcelona, 08035, Spain.
Jazyk:	angličtina
Zdroj:	Therapeutic advances in medical oncology [Ther Adv Med Oncol] 2021 Jan 07; Vol. 13, pp. 1758835920986498. Date of Electronic Publication: 2021 Jan 07 (Print Publication: 2021).
DOI:	10.1177/1758835920986498
Abstrakt:	Gastrointestinal stromal tumor (GIST) represents a paradigm for clinically effective targeted inhibition of oncogenic driver mutations in cancer. Five drugs are currently positioned as the standard of care for the treatment of advanced or metastatic GIST patients. This is the result of continuous, deep understanding of KIT and PDGFRA GIST oncogenic drivers as well as the resistance mechanisms associated to tumor progression. However, the complexity of GIST molecular heterogeneity is an evolving field, and critical questions remain open. Specifically, the clinical benefit of approved and/or investigated targeted agents is strikingly modest at advanced stages of the disease when compared with the activity of first-line imatinib. Ripretinib is a novel switch-pocket inhibitor with broad activity against KIT and PDGFRA oncoproteins and has recently demonstrated antitumoral activity across phase I to phase III clinical trials. Therefore, ripretinib has emerged as a new standard of care for advanced, multi-resistant GIST patients. Based on this data, the Food and Drug Administration has granted in 2020 the approval of ripretinib for GIST patients after progression to imatinib, sunitinib and regorafenib. This, in turn, constitutes a major breakthrough in sarcoma drug development, as there have not been new treatment approvals in GIST for nearly a decade. Herein, we provide a critical review on the preclinical and clinical development of ripretinib in GIST. Furthermore, we seek to assess the biological and clinical impact of this new standard of care on the course of the disease, aiming to provide an insight on future treatments strategies for the next coming years. Competing Interests: Conflict of interest statement: C.S. has received research funding from Deciphera Pharmaceuticals, Karyopharm, Bayer AG and Pfizer, Inc; consulting fees (advisory role) from Deciphera Pharmaceuticals and Blueprint Medicines; payment for lectures from Bayer AG and Blueprint Medicines; and travel grants from Pharmamar, Pfizer, Bayer AG, Novartis and Lilly. C.V. research grants from Lilly, Novartis, Pfizer, Pharmamar, Karyopharm, Incyte, Adaptimmune, and GlaxoSmithKline; consulting fees (advisory role) from Lilly, Pharmamar, Pfizer, Eisai, Bayer, MundiPharma, and GlaxoSmithKline; and travel grants from Pharmamar, Lilly, Novartis, Pfizer, and Bayer. The remaining authors declare no conflicts of interests. (© The Author(s), 2021.)
Databáze:	MEDLINE
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