Target therapy for BRAF mutated anaplastic thyroid cancer: a clinical and molecular study

Area of Science:

• Oncology
• Molecular Biology
• Clinical Medicine

Background:

• Anaplastic thyroid carcinoma (ATC) is an aggressive cancer with historically poor prognosis.
• Targeted therapy, such as Dabrafenib plus Trametinib (DT), has shown promise for BRAF p.V600E-mutated ATC.
• Understanding treatment outcomes and resistance mechanisms is crucial for improving patient survival.

Purpose of the Study:

• To evaluate the real-world efficacy and safety of Dabrafenib plus Trametinib (DT) in BRAF-mutated anaplastic thyroid carcinoma (ATC) patients.
• To compare outcomes of DT treatment with standard multimodal therapy (MT) and compassionate care (CC) in BRAF wild-type (WT) ATC.
• To investigate molecular alterations associated with treatment resistance in the DT group.

Main Methods:

• Retrospective analysis of 27 ATC patients treated between May 2018 and April 2022.
• Patients categorized into three groups: BRAF p.V600E treated with DT, BRAF WT under MT, and BRAF WT under CC.
• Overall survival (OS) and progression-free survival (PFS) assessed using Kaplan-Meier method and compared with log-rank test; response evaluated per RECIST 1.1.

Main Results:

• DT group (n=9) showed significantly longer median OS (475 days) and PFS (270 days) compared to MT (156 days OS, <32 days PFS) and CC (<39 days OS, <32 days PFS) groups (P < .001).
• At 12 months, 71% of patients in the DT group were alive, while none were in the WT groups.
• No severe adverse events were reported with DT; one case of progression revealed an NRAS mutation.

Conclusions:

• Dabrafenib plus Trametinib (DT) demonstrates significant real-world efficacy in improving survival and reducing recurrence for BRAF-mutated ATC.
• The combination therapy exhibits a favorable safety profile in clinical practice.
• Further molecular studies are warranted to understand resistance mechanisms, such as NRAS mutations.