Dabrafenib plus trametinib treatment in patients with anaplastic thyroid carcinoma: an Argentinian experience

Abstract

Purpose: To present our real-life experience with dabrafenib and trametinib (D-T) treatment in patients with BRAF V600E-mutated ATC in Argentina.

Patients y methods: We included five patients from four different hospitals. The median age was 70 years, and 60% were male. The performance status at diagnosis was grade 0 in 60% and grade 2 in 40% of patients. Four patients could undergo total thyroidectomy; in one of them, surgical treatment was amenable due to the indication of D-T as neoadjuvant therapy. From the total cohort, the best response to treatment was complete response in 40%, partial response in 20%, and stable disease in 20%. The median duration of response was 20 weeks, ranging from 16 to 92 weeks. All patients experienced at least one adverse event (AE). Grade ≥3 AEs were observed in two (40%) patients. They were upper gastrointestinal bleeding and subclavian vein thrombosis. The median follow-up was 20 weeks (range: 16 to 92).

Conclusion: This report contributes to illustrate the feasibility and effectiveness of D-T treatment in five patients with loco-regionally advanced and metastatic BRAF V600E-mutated ATC in a real-life setting. A multidisciplinary approach and rapid molecular-tailored testing are essential to begin this therapeutic option.

Keywords: Anaplastic thyroid carcinoma; Dabrafenib; Real-life experience; Targeted therapy; Trametinib.

Fig. 1

Lesion outcome under treatment with D-T. a Before treatment. b After one day of treatment. c After four days of treatment. d After seven days of treatment. e After ten days of treatment. f After four weeks of D-T treatment

Fig. 2

a, b Axial view of Computed Tomography (CT) scans of the neck showing a 12 x 13 cm cervical mass in the thyroid and left lateral neck before treatment. c, d Four weeks after treatment, the axial view of CT scans showed a reduction of nearly 95% in the cervical mass

Fig. 3

Large cervical mass extending to the left side and lung metastasis. Axial view of Computed Tomography scans of the neck showing a partial response of the primary lesion and lung metastasis. a, b Before treatment: mass in the thyroid and left lateral neck of 12 x 10 x 8 cm. c. Dominant lung nodule of 1 x 0.9 cm (arrow). Twelve weeks after treatment: d, e The mass was stable with a slight growth to 9.6 x 6.8 x 5 cm. f The lung nodule of 0.6 cm with a reduction of 60% compared to the initial diameter

Fig. 4

Axial view of Computed Tomography scan of the neck showing the cervical mass

Fig. 5

Waterfall chart of percentage change in the longest diameter of the target lesions from baseline under D-T treatment (n = 5). D–T, dafrafenib and trametinib

Fig. 6

Duration of overall response in the cohort

Fig. 7

Kaplan–Meier analysis of overall survival in the cohort