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Endocrine cancer
Combination of Dabrafenib and Trametinib in Patients with Metastatic BRAFV600E-Mutated Thyroid Cancer
Youngkyung Jeon, Sehhoon Park, Se-Hoon Lee, Tae Hyuk Kim, Sun Wook Kim, Myung-Ju Ahn, Hyun Ae Jung, Jae Hoon Chung
Cancer Res Treat. 2024;56(4):1270-1276.   Published online March 6, 2024
DOI: https://doi.org/10.4143/crt.2023.1278
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
BRAF mutations are detected in 30%-80% of papillary thyroid cancer (PTC) cases. DaBRAFenib and trametinib showed promising antitumor activity in patients with BRAFV600E-mutated metastatic melanoma and non–small cell lung cancer. This study aimed to evaluate the efficacy and safety of daBRAFenib and trametinib in patients with metastatic BRAFV600E-mutated thyroid cancer.
Materials and Methods
This was a retrospective study to evaluate the efficacy of daBRAFenib and trametinib in patients with metastatic BRAFV600E-mutated PTC. The patients received daBRAFenib 150 mg twice daily and trametinib 2 mg once daily at the Samsung Medical Center. This study evaluated the progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) overall survival (OS), and safety of daBRAFenib and trametinib.
Results
Between December 2019 and January 2022, 27 PTC patients including eight patients with poorly differentiated or anaplastic transformation, received daBRAFenib and trametinib. The median age was 73.0 years, and the median follow-up period was 19.8 months. The majority (81.5%) had undergone thyroidectomy, while 8 patients had received prior systemic treatments. ORR was 73.1%, with 19 partial responses, and DCR was 92.3%. Median PFS was 21.7 months, and median OS was 21.7 months. Treatment-related adverse events included generalized weakness (29.6%), fever (25.9%), and gastrointestinal problems (22.2%). Dose reduction due to adverse events was required in 81.5% of the patients.
Conclusion
DaBRAFenib and trametinib demonstrated a high ORR with promising PFS; however, most patients with BRAFV600E-mutated metastatic PTC required a dose reduction.

Citations

Citations to this article as recorded by  
  • Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part III. Management of Advanced Differentiated Thyroid Cancers - Chapter 4. Systemic Therapy for Progressive Radioiodine-Refractory Differentiated Thyroid Cancer 2
    Dong Yeob Shin, Ho-Cheol Kang, Sun Wook Kim, Dong Gyu Na, Young Joo Park, Young Shin Song, Eun Kyung Lee, Dong-Jun Lim, Yun Jae Chung, Won Gu Kim
    International Journal of Thyroidology.2024; 17(1): 168.     CrossRef
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    Silvia Martina Ferrari, Francesca Ragusa, Giusy Elia, Valeria Mazzi, Eugenia Balestri, Chiara Botrini, Licia Rugani, Armando Patrizio, Simona Piaggi, Concettina La Motta, Salvatore Ulisse, Camilla Virili, Alessandro Antonelli, Poupak Fallahi
    International Journal of Molecular Sciences.2024; 25(12): 6734.     CrossRef
  • The Long Journey towards Personalized Targeted Therapy in Poorly Differentiated Thyroid Carcinoma (PDTC): A Case Report and Systematic Review
    Odysseas Violetis, Panagiota Konstantakou, Ariadni Spyroglou, Antonios Xydakis, Panagiotis B. Kekis, Sofia Tseleni, Denise Kolomodi, Manousos Konstadoulakis, George Mastorakos, Maria Theochari, Javier Aller, Krystallenia I. Alexandraki
    Journal of Personalized Medicine.2024; 14(6): 654.     CrossRef
  • Treatment of Unresectable BRAF V600E, TERT-Mutated Differentiated Papillary Thyroid Cancer With Dabrafenib and Trametinib
    Neha Bapat, Tatiana Ferraro, Layal Esper, Arjun S Joshi, Faysal Haroun, Chelsey K Baldwin
    JCEM Case Reports.2024;[Epub]     CrossRef
  • Trametinib

    Reactions Weekly.2024; 2035(1): 467.     CrossRef
  • 2,776 View
  • 383 Download
  • 2 Web of Science
  • 5 Crossref
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Pediatric cancer
Effectiveness and Safety of Dabrafenib in the Treatment of 20 Chinese Children with BRAFV600E-Mutated Langerhans Cell Histiocytosis
Ying Yang, Dong Wang, Lei Cui, Hong-Hao Ma, Li Zhang, Hong-Yun Lian, Qing Zhang, Xiao-Xi Zhao, Li-Ping Zhang, Yun-Ze Zhao, Na Li, Tian-You Wang, Zhi-Gang Li, Rui Zhang
Cancer Res Treat. 2021;53(1):261-269.   Published online September 15, 2020
DOI: https://doi.org/10.4143/crt.2020.769
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We sought to investigate the effectiveness and safety of dabrafenib in children with BRAFV600E-mutated Langerhans cell histiocytosis (LCH).
Materials and Methods
A retrospective analysis was performed on 20 children with BRAFV600E-mutated LCH who were treated with dabrafenib.
Results
The median age at which the patients started taking dabrafenib was 2.3 years old (range, 0.6 to 6.5 years). The ratio of boys to girls was 2.3:1. The median follow-up time was 30.8 months (range, 18.9 to 43.6 months). There were 14 patients (70%) in the risk organ (RO)+ group and six patients (30%) in the RO group. All patients were initially treated with traditional chemotherapy and then shifted to targeted therapy due to poor control of LCH or intolerance to chemotherapy. The overall objective response rate and the overall disease control rate were 65% and 75%, respectively. During treatment, circulating levels of cell-free BRAFV600E (cfBRAFV600E) became negative in 60% of the patients within a median period of 3.0 months (range, 1.0 to 9.0 months). Grade 2 or 3 adverse effects occurred in five patients.
Conclusion
Some children with BRAFV600E-mutated LCH may benefit from monotherapy with dabrafenib, especially high-risk patients with concomitant hemophagocytic lymphohistiocytosis and intolerance to chemotherapy. The safety of dabrafenib is notable. A prospective study with a larger sample size is required to determine the optimal dosage and treatment duration.

Citations

Citations to this article as recorded by  
  • Genetic Landscape and Its Prognostic Impact in Children With Langerhans Cell Histiocytosis
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    Archives of Pathology & Laboratory Medicine.2025; 149(2): 175.     CrossRef
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    Emmanuel Lee Boniao, Richard C. Allen, Gangadhara Sundar
    Orbit.2024; 43(5): 656.     CrossRef
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    BMC Pediatrics.2024;[Epub]     CrossRef
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    Jiaying Lei, Wenxia Wang, Danna Lin, Chengguang Zhu, Wenguang Jia, Wenjun Weng, Xiaoshan Liu, Yuhan Ma, Zhixuan Wang, Lihua Yang, Xiangling He, Yunyan He, Yang LI
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    Xue-Lian Wang, Chun-Xiao Fang, Min-Xia Chen, Hua-Mei Yang, Lan-Hui She, Yu Gong, Yi Xu, Wei-Qiang Xiao, Jin-Sheng Tian, Bin Ai, Li Huang, Xu-Fang Li
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    延泽 刘
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  • Improvement in Pituitary Imaging After Targeted Therapy in Three Children with BRAF-Mutated Langerhans Cell Histiocytosis with Pituitary Involvement


    Ying Yang, Dong Wang, Na Li, Honghao Ma, Hongyun Lian, Lei Cui, Qing Zhang, Xiaoxi Zhao, Liping Zhang, Yunze Zhao, Chanjuan Wang, Li Zhang, Tianyou Wang, Zhigang Li, Rui Zhang
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  • 34,885 View
  • 234 Download
  • 19 Web of Science
  • 25 Crossref
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