Anaplastic Thyroid Carcinoma With Cardiac Dysfunction Developed During Combination Therapy With Dabrafenib and Trametinib

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive malignancies and is associated with an extremely poor prognosis. Multimodal therapy, combining surgery, radiation therapy, and chemotherapy, is recommended. Although paclitaxel and lenvatinib have been used as drug treatments, combination therapy with dabrafenib and trametinib has recently been reported to be effective. This combination therapy is generally associated with few serious adverse events, although rare cases of cardiac dysfunction have been reported. Here, we report the case of an 84-year-old woman with BRAF V600E mutation-positive ATC who developed cardiac dysfunction during combination therapy with dabrafenib and trametinib. The patient had no significant medical history and was referred to our department with left vocal cord paralysis and a thyroid mass. Histological examination of the right thyroid lobe tumor revealed components of undifferentiated carcinoma. Imaging studies showed invasion of the larynx and trachea, leading to total thyroidectomy, total laryngectomy, and paratracheal lymph node dissection. Postoperative pathological examination confirmed ATC (pT4aN0). Postoperative imaging revealed no distant metastases, and adjuvant radiotherapy was administered. Four months after the completion of radiotherapy, a cervical lymph node recurrence and right lung metastases were observed. As the tumor tested positive for BRAF V600E mutation using the MEBGEN™ BRAF kit, combination therapy with dabrafenib and trametinib was initiated. At week five of treatment, pitting edema developed in both lower limbs, and a decrease in the left ventricular ejection fraction (LVEF) was noted, prompting the discontinuation of therapy. By week six, the LVEF recovered, and dabrafenib was restarted at the same dose, whereas trametinib was resumed at a one-step reduced dose. Follow-up CT at week six demonstrated a partial response (PR). Treatment was continued at these doses; however, tumor enlargement was observed at week 26, leading to treatment discontinuation and a transition to palliative care. ATC remains extremely challenging to treat because of its rapid progression and low sensitivity to drug therapies. Furthermore, lenvatinib, a molecularly targeted agent, shows limited efficacy against ATC and is associated with frequent adverse events. In contrast, combination therapy with dabrafenib and trametinib is considered an effective therapeutic option for patients with BRAF V600E mutation-positive ATC, when appropriate management and monitoring are implemented.