Chen Yen-Hao, Chou Chen-Kai, Chi Shun-Yu, Chang Yen-Hsiang, Wang Pei-Wen, Chan Yi-Chia
Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung 833, Taiwan.
School of Medicine, College of Medicine, Chang Gung University Taoyuan 333, Taiwan.
Am J Cancer Res. 2025 Aug 15;15(8):3524-3532. doi: 10.62347/WFPD3948. eCollection 2025.
BRAF V600E is the most common oncogenic mutation in papillary thyroid carcinoma (PTC). This study aimed to assess the clinical outcomes of combining dabrafenib and trametinib in patients with BRAF V600E-mutant PTC. Patients with BRAF V600E-mutant PTC treated with dabrafenib and trametinib in either first-line or second-line settings were included. Dabrafenib was administered orally at 150 mg twice daily, alongside trametinib at 2 mg once daily. Response was determined using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A total of 71 PTC patients who received systemic therapy were identified, including 21 patients who experienced dabrafenib plus trametinib. For these 21 patients, the objective response rate (ORR) was 66.7%, with a disease control rate (DCR) of 85.7%. In the first-line setting, the ORR and DCR were higher at 75.0% and 91.7%, respectively. The median progression-free survival (PFS) was 40.7 months, and the overall survival (OS) was 47.7 months. While patients treated in the first-line setting (n=12) showed better PFS (40.7 months vs. 18.9 months) and OS (47.7 months vs. 39.4 months) compared to those treated in the second-line setting (n=9), the differences were not statistically significant. Moreover, in the first-line treatment, 12 patients received dabrafenib plus trametinib, while 59 patients were treated with lenvatinib; no significant differences in PFS or OS were observed between the two groups. Most adverse events related to the combination therapy were grade 1-2, with no grade 3-4 toxicities reported. Additionally, most patients (75.0%) were able to receive subsequent treatments following disease progression to this combination therapy. The findings of current study highlight the efficacy and safety of dabrafenib combined with trametinib in patients with BRAF V600E-mutant PTC, particularly as a first-line treatment. These findings suggest a promising therapeutic option for this patient population.
BRAF V600E是乳头状甲状腺癌（PTC）中最常见的致癌突变。本研究旨在评估达拉非尼和曲美替尼联合治疗BRAF V600E突变型PTC患者的临床疗效。纳入在一线或二线治疗中接受达拉非尼和曲美替尼治疗的BRAF V600E突变型PTC患者。达拉非尼口服给药，剂量为150 mg，每日两次，同时曲美替尼剂量为2 mg，每日一次。使用实体瘤疗效评价标准（RECIST）1.1版确定疗效。共确定71例接受全身治疗的PTC患者，其中21例接受达拉非尼加曲美替尼治疗。对于这21例患者，客观缓解率（ORR）为66.7%，疾病控制率（DCR）为85.7%。在一线治疗中，ORR和DCR更高，分别为75.0%和91.7%。中位无进展生存期（PFS）为40.7个月，总生存期（OS）为47.7个月。与二线治疗的患者（n=9）相比，一线治疗的患者（n=12）显示出更好的PFS（40.7个月对18.9个月）和OS（47.7个月对39.4个月），但差异无统计学意义。此外，在一线治疗中，12例患者接受达拉非尼加曲美替尼治疗，59例患者接受乐伐替尼治疗；两组之间在PFS或OS方面未观察到显著差异。大多数与联合治疗相关的不良事件为1-2级，未报告3-4级毒性反应。此外，大多数患者（75.0%）在疾病进展至该联合治疗后能够接受后续治疗。本研究结果突出了达拉非尼联合曲美替尼治疗BRAF V600E突变型PTC患者的疗效和安全性，尤其是作为一线治疗。这些发现为该患者群体提供了一个有前景的治疗选择。
