Ahn Jin-Hee, Lee Jeeyun, Park Changhee, Beom Seung-Hoon, Kim Seung Hyun, Lee Young Han, Yun Kum-Hee, Kim Jeung Eun, Baek Wooyeol, Han Yoon Dae, Kim Sang Kyum, Ryu Hyang Joo, Jung Inkyung, Lee JooHee, Yoon Hong In, Kim Hyo Song
Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Clin Cancer Res. 2024 Apr 15;30(8):1457-1465. doi: 10.1158/1078-0432.CCR-23-2823.
The study was to determine the activity and safety of the TGF-β inhibitor vactosertib in combination with imatinib in patients with desmoid tumors.
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.
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%).
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.
本研究旨在确定转化生长因子-β（TGF-β）抑制剂维托西妥单抗联合伊马替尼治疗韧带样型纤维瘤病患者的活性和安全性。
在这项由研究者发起的、开放标签、多中心、Ib/II期试验中，纳入了不适用于局部区域治疗（手术和/或放疗）或至少接受过一种治疗后疾病进展的韧带样型纤维瘤病患者。参与者每28天接受一次治疗，每天服用400 mg伊马替尼，并联合维托西妥单抗（连续服用5天，停药2天，每日两次）。在Ib期，维托西妥单抗剂量设定为100 mg（-1级）和200 mg（1级），以确定推荐的II期剂量（RP2D）。II期评估疗效，主要终点为16周时的无进展率（PFR）。
在Ib期未观察到剂量限制性毒性；因此，RP2D定义为每日400 mg伊马替尼联合200 mg维托西妥单抗。在评估的27例患者中，7例（25.9%）达到确认的部分缓解，19例（70.4%）病情稳定。16周和1年时的PFR分别为96.3%和81.0%。大多数毒性为轻度至中度肌痛（n = 10，37%）、贫血（n = 10，37%）和恶心（n = 9，33.3%）。常见的3至4级毒性包括中性粒细胞减少（n = 6，22.2%）和贫血（n = 5, 18.5%）。
维托西妥单抗与伊马替尼联合用药耐受性良好，在进展性、局部晚期韧带样型纤维瘤病患者中具有良好的临床活性。这是第一项在这种罕见且难以治疗的韧带样型纤维瘤病中研究新型靶向药物（一种TGF-β抑制剂）的研究。
