Cancer Res Treat.  2024 Oct;56(4):1270-1276. 10.4143/crt.2023.1278.

Combination of Dabrafenib and Trametinib in Patients with Metastatic BRAF^V600E-Mutated Thyroid Cancer

• Jeon Y
• Park S
• Lee SH
• Kim TH
• Kim SW
• Ahn MJ
• Jung HA
• Chung JH

• KMID: 2560260
• DOI: http://doi.org/10.4143/crt.2023.1278

Abstract

Purpose
BRAF mutations are detected in 30%-80% of papillary thyroid cancer (PTC) cases. DaBRAFenib and trametinib showed promising antitumor activity in patients with BRAF^V600E-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 BRAF^V600E-mutated thyroid cancer.
Materials and Methods
This was a retrospective study to evaluate the efficacy of daBRAFenib and trametinib in patients with metastatic BRAF^V600E-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 BRAF^V600E-mutated metastatic PTC required a dose reduction.

Keyword

Thyroid neoplasms; Dabrafenib; Trametinib

Figure

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  Fig. 1. Waterfall plot. PD, progressive disease; PR, partial response; SD, stable disease.

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  Fig. 2. Kaplan-Meier curves for progression-free survival in all study population (A), lines of therapy (B), and histology (C). CI, confidence interval; P/D, poorly differentiated; PTC, papillary thyroid cancer.

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  Fig. 3. Kaplan-Meier curves for overall survival in all study population (A), lines of therapy (B), and histology (C). CI, confidence interval; P/D, poorly differentiated; PTC, papillary thyroid cancer.

Reference

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