1930P - Resensitization of BRAF-mutated radioactive iodine refractory differentiated thyroid cancer with longer duration of dabrafenib and trametinib

Background

Iodine refractory differentiated thyroid cancer (DTC) carries a poor prognosis. BRAF/MEK/MAPK pathway activation is associated with loss of expression of iodine-metabolizing genes in thyroid cancer, resulting in iodine refractoriness. BRAF, MEK inhibitors have previously been shown to resensitize iodine refractory DTC in small clinical trials, however, the optimal drug/drug combination and duration of resensitization remain to be elucidated.

Methods

This is a single-center, retrospective study of resensitization of BRAF-mutated iodine-refractory DTC using both dabrafenib and trametinib (DT) between January 2020 and April 2024. Successful resensitization was defined as significant uptake of ¹³¹I on the posttreatment whole body scan (WBS); median duration of response was calculated from initiation of RAI treatment. Duration of resensitization, thyroglobulin levels were also collected.

Results

A total of 19 patients were included in the final analysis, with median age of 66 years, 53% (10/19) females, and 58% (11/19) Caucasian, 32% (6/19) Hispanic and 10% (2/19) Native American. All patients were confirmed to have BRAF V600E mutation; 84% (16/19) had distant metastasis; 84% (16/19) had baseline WBS without iodine uptake; 16% (3/19) had progression of disease 3 months after the previous RAI ablation. Median duration of resensitization was 6 months (range 3-16); 90% (17/19) of patients achieved successful resensitization. Of note, 4 patients did not resensitize at 6 to 12 weeks but after 6 months. Interestingly, for patients without baseline thyroglobulin antibody, marked elevation of thyroglobulin level correlated very well with successful resensitization in 80% (12/15) of patients. At median follow-up of 10 months (range 1-33), no patients with successful resensitization had progression of disease. Combination of DT were well tolerated, 5 patients experienced severe confusion, renal failure or hyponatremia, requiring dose reduction of dabrafenib, but were able to complete the treatment.

Conclusions

Longer duration of dabrafenib and trametinib appears to be safe and more effective on resensitization of BRAF-mutated iodine refractory DTC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

J.J. Niu: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, G1 Therapeutics, Mirati Therapeutics, Pfizer, Sanofi. All other authors have declared no conflicts of interest.