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Updated: Jul 1, 2025
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Combination of Dabrafenib and Trametinib in Patients with Metastatic BRAFV600E-Mutated Thyroid Cancer
Youngkyung Jeon1, Sehhoon Park1, Se-Hoon Lee1
1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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.
Insights
Dabrafenib and trametinib showed significant efficacy in treating BRAFV600E-mutated papillary thyroid cancer (PTC), achieving high response rates and prolonged progression-free survival. However, most patients required dose reductions due to adverse events.
Area of Science:
- Oncology
- Molecular targeted therapy
- Thyroid cancer research
Background:
- BRAF mutations are common in papillary thyroid cancer (PTC), affecting 30%-80% of cases.
- Dabrafenib and trametinib have demonstrated efficacy in other cancers with BRAFV600E mutations.
- Evaluating targeted therapy for metastatic BRAFV600E-mutated PTC is crucial.
Purpose of the Study:
- To assess the efficacy and safety of dabrafenib and trametinib in patients with metastatic BRAFV600E-mutated PTC.
- To determine progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and overall survival (OS).
- To document treatment-related adverse events and the need for dose modifications.
Main Methods:
- Retrospective analysis of 27 metastatic BRAFV600E-mutated PTC patients treated with dabrafenib and trametinib.
- Standard dosing: dabrafenib 150 mg twice daily and trametinib 2 mg once daily.
- Evaluation of efficacy endpoints (PFS, ORR, DCR, OS) and safety profile.
Main Results:
- High objective response rate (ORR) of 73.1% and disease control rate (DCR) of 92.3%.
- Median progression-free survival (PFS) and overall survival (OS) of 21.7 months.
- Most patients (81.5%) required dose reduction due to adverse events like weakness and fever.
Conclusions:
- Dabrafenib and trametinib exhibit significant antitumor activity and promising PFS in metastatic BRAFV600E-mutated PTC.
- High incidence of dose reduction due to adverse events necessitates careful patient monitoring and management.
- Targeted therapy offers a viable option for this patient population, despite tolerability challenges.
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