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
Antineoplastic Effect of ALK Inhibitor Crizotinib in Primary Human Anaplastic Thyroid Cancer Cells with STRN–ALK Fusion In Vitro 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
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 Chan-Juan Wang, Lei Cui, Shuang-Shuang Li, Hong-Hao Ma, Dong Wang, Hong-Yun Lian, Yun-Ze Zhao, Li-Ping Zhang, Wei-Jing Li, Qing Zhang, Xiao-Xi Zhao, Ying Yang, Xiao-Tong Huang, Wei Liu, Yi-Zhuo Wang, Wan-Shui Wu, Tian-You Wang, Rui Zhang, Zhi-Gang Li Archives of Pathology & Laboratory Medicine.2025; 149(2): 175. CrossRef
Targeted therapy and immunotherapy for orbital and periorbital tumors: a major review Emmanuel Lee Boniao, Richard C. Allen, Gangadhara Sundar Orbit.2024; 43(5): 656. CrossRef
Treatment of children with refractory/relapse high risk langerhans cell histiocytosis with the combination of cytarabine, vindesine and prednisone Wenqian Wang, Jian Ge, Honghao Ma, Hongyun Lian, Lei Cui, Yunze Zhao, Zhigang Li, Tianyou Wang, Rui Zhang BMC Pediatrics.2024;[Epub] CrossRef
Vemurafenib combined with chemotherapy achieved sustained remission in pediatric LCH: a multi-center observational study 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 Journal of Cancer Research and Clinical Oncology.2024;[Epub] CrossRef
Clinical features and treatment outcomes of liver involvement in paediatric Langerhans cell histiocytosis Xinshun Ge, Wenxin Ou, Ang Wei, Hongyun Lian, Honghao Ma, Lei Cui, Dong Wang, Liping Zhang, Xiaoman Wang, Lejian He, Rui Zhang, Tianyou Wang BMC Pediatrics.2024;[Epub] CrossRef
Refractory juvenile xanthogranuloma of the mastoid bone responsive to trametinib Isaac Hauk, Ignacio Gonzalez‐Gomes, Deepak Chellapandian, Jonathan Metts, Peter H. Shaw Pediatric Blood & Cancer.2024;[Epub] CrossRef
Advancements in the understanding and management of histiocytic neoplasms Kyung-Nam Koh, Su Hyun Yoon, Sung Han Kang, Hyery Kim, Ho Joon Im Blood Research.2024;[Epub] CrossRef
Real-world experience with targeted therapy in patients with histiocytic neoplasms in the Netherlands and in Belgium Paul G. Kemps, F. J. Sherida H. Woei-A-Jin, Patrick Schöffski, Thomas Tousseyn, Isabelle Vanden Bempt, Friederike A. G. Meyer-Wentrup, Natasja Dors, Natasha K. A. van Eijkelenburg, Marijn A. Scheijde-Vermeulen, Ingrid M. Jazet, Maarten Limper, Margot Jak, Blood Neoplasia.2024; 1(3): 100023. CrossRef
The clinical impact of serum soluble CD25 levels in children with Langerhans cell histiocytosis Zi-Jing Zhao, Hong-Yun Lian, Wei-Jing Li, Qing Zhang, Hong-Hao Ma, Dong Wang, Yun-Ze Zhao, Ting Zhu, Hua-Lin Li, Xiao-Tong Huang, Tian-You Wang, Rui Zhang, Lei Cui, Zhi-Gang Li Jornal de Pediatria.2024;[Epub] CrossRef
Liver transplantation in a child with sclerosing cholangitis due to Langerhans cell histiocytosis: a case report 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 Frontiers in Pediatrics.2024;[Epub] CrossRef
BRAF V600E gene mutation is present in primary intraosseous Rosai-Dorfman disease Lokman Cevik, Swati Satturwar, Dan Jones, Joel Mayerson, Steve Oghumu, O. Hans Iwenofu Human Pathology.2024; 154: 105702. CrossRef
Langerhans cell histiocytosis as a clonal disease of mononuclear phagocyte system Evgeniy F. Khynku, Maria K. Monaenkova, Olga B. Tamrazova, Alexey V. Taganov, Мarina А. Gureeva, Gayane E. Bagramova, Anton V. Molochkov Almanac of Clinical Medicine.2023; 50(7): 428. CrossRef
Lineage switching of the cellular distribution of BRAF
V600E in multisystem Langerhans cell histiocytosis Paul Milne, Simon Bomken, Olga Slater, Ashish Kumar, Adam Nelson, Somak Roy, Jessica Velazquez, Kshitij Mankad, James Nicholson, Dan Yeomanson, Richard Grundy, Ahmed Kamal, Anthony Penn, Jane Pears, Gerard Millen, Bruce Morland, James Hayden, Jason Lam, M Blood Advances.2023; 7(10): 2171. CrossRef
Treatment of Langerhans Cell Histiocytosis and Histiocytic Disorders: A Focus on MAPK Pathway Inhibitors Ashley V. Geerlinks, Oussama Abla Pediatric Drugs.2023; 25(4): 399. CrossRef
Dabrafenib, alone or in combination with trametinib, in BRAF V600–mutated pediatric Langerhans cell histiocytosis James A. Whitlock, Birgit Geoerger, Ira J. Dunkel, Michael Roughton, Jeea Choi, Lisa Osterloh, Mark Russo, Darren Hargrave Blood Advances.2023; 7(15): 3806. CrossRef
Therapiestrategien bei Kindern und Jugendlichen mit Langerhanszell
Histiozytosen Anke Elisabeth Barnbrock, Caroline Hutter, Konrad Bochennek, Milen Minkov, Thomas Lehrnbecher Klinische Pädiatrie.2023; 235(06): 342. CrossRef
Mutant PIK3CA is a targetable driver alteration in histiocytic neoplasms Benjamin H. Durham, Oshrat Hershkovitz-Rokah, Omar Abdel-Wahab, Mariko Yabe, Young Rock Chung, Gilad Itchaki, Maayan Ben-Sasson, Vered A. Asher-Guz, David Groshar, Seyram A. Doe-Tetteh, Tina Alano, David B. Solit, Ofer Shpilberg, Eli L. Diamond, Roei D. M Blood Advances.2023; 7(23): 7319. CrossRef
Validation of Liquid Chromatography Coupled with Tandem Mass Spectrometry for the Determination of 12 Tyrosine Kinase Inhibitors (TKIs) and Their Application to Therapeutic Drug Monitoring in Adult and Pediatric Populations Marie Bellouard, Jean Donadieu, Pauline Thiebot, Etienne Giroux Leprieur, Philippe Saiag, Isabelle Etting, Pamela Dugues, Emuri Abe, Jean-Claude Alvarez, Islam-Amine Larabi Pharmaceutics.2023; 16(1): 5. CrossRef
Langerhans cell histiocytosis: promises and caveats of targeted therapies in high-risk and CNS disease Oussama Abla Hematology.2023; 2023(1): 386. CrossRef
Characteristics and Treatment Outcomes of Pediatric Langerhans Cell Histiocytosis with Thymic Involvement Ja-Feng Yao, Dong Wang, Hong-Hao Ma, Hong-Yun Lian, Li Zhang, Tian-You Wang, Zhi-Gang Li, Jin Jiang, Lei Cui, Rui Zhang The Journal of Pediatrics.2022; 244: 194. CrossRef
Clinical features and treatment outcomes of pediatric Langerhans cell histiocytosis with macrophage activation syndrome-hemophagocytic lymphohistiocytosis Dong Wang, Xi-Hua Chen, Ang Wei, Chun-Ju Zhou, Xue Zhang, Hong-Hao Ma, Hong-Yun Lian, Li Zhang, Qing Zhang, Xiao-Tong Huang, Chan-Juan Wang, Ying Yang, Wei Liu, Tian-You Wang, Zhi-Gang Li, Lei Cui, Rui Zhang Orphanet Journal of Rare Diseases.2022;[Epub] CrossRef
Current perspectives on the role of liver transplantation for Langerhans cell histiocytosis: A narrative review Jagadeesh Menon, Ashwin Rammohan, Mukul Vij, Naresh Shanmugam, Mohamed Rela World Journal of Gastroenterology.2022; 28(30): 4044. CrossRef
Research Progress of BRAF V600E Gene Mutation in Papillary Thyroid Carcinoma 延泽 刘 Advances in Clinical Medicine.2022; 12(09): 8499. CrossRef
Recent advances in the understanding of the molecular pathogenesis and targeted therapy options in Langerhans cell histiocytosis Jin Kyung Suh, Sunghan Kang, Hyery Kim, Ho Joon Im, Kyung-Nam Koh BLOOD RESEARCH.2021; 56(S1): S65. CrossRef
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 OncoTargets and Therapy.2020; Volume 13: 12357. CrossRef