Clinical Activity of TGF-β Inhibitor Vactosertib in Combination with Imatinib in Desmoid Tumors: A Multicenter Phase Ib/II Study.

Autor:	Ahn JH; Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea., Lee J; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., Park C; Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea., Beom SH; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea., Kim SH; Department of Orthopedic Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea., Lee YH; Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea., Yun KH; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea., Kim JE; Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea., Baek W; Department of Plastic Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea., Han YD; Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea., Kim SK; Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea., Ryu HJ; Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea., Jung I; Division of Biostatistics, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea., Lee J; Department of Orthopedic Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea., Yoon HI; Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea., Kim HS; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Apr 15; Vol. 30 (8), pp. 1457-1465.
DOI:	10.1158/1078-0432.CCR-23-2823
Abstrakt:	Purpose: The study was to determine the activity and safety of the TGF-β inhibitor vactosertib in combination with imatinib in patients with desmoid tumors. Patients and Methods: In this investigator-initiated, open-label, multicenter, phase Ib/II trial, patients with desmoid tumors not amenable to locoregional therapies (surgery and/or radiotherapy) or with disease progression following at least one treatment were enrolled. Participants were administered 400 mg imatinib daily in combination with vactosertib (5 days on and 2 days off, twice a day) every 28 days. In phase Ib, the vactosertib dose was set at 100 mg (level -1) and 200 mg (level 1) to determine the recommended phase II dose (RP2D). Phase II assessed the efficacy, with the primary endpoint being progression-free rate (PFR) at 16 weeks. Results: No dose-limiting toxicities were observed during phase Ib; therefore RP2D was defined at doses of 400 mg imatinib daily in combination with 200 mg vactosertib. Of the 27 patients evaluated, 7 (25.9%) achieved a confirmed partial response and 19 (70.4%) were stable. The PFR at 16 weeks and 1 year were 96.3% and 81.0%, respectively. Most toxicities were mild to moderate myalgia (n = 10, 37%), anemia (n = 10, 37%), and nausea (n = 9, 33.3%). Common grade 3 to 4 toxicities included neutropenia (n = 6, 22.2%) and anemia (n = 5, 18.5%). Conclusions: The vactosertib and imatinib combination was well tolerated, with promising clinical activity in patients with progressive, locally advanced desmoid tumors. This is the first study investigating a novel target agent, a TGF-β inhibitor, in this rare and difficult-to-treat desmoid tumor. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
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