The aim of this study was to describe the oncologic outcomes of patients with BRAF
-mutated anaplastic thyroid cancer (ATC) who had neoadjuvant BRAF-directed therapy with subsequent surgery. For ...context, we also reviewed patients who received BRAF-directed therapy after surgery, and those who did not have surgery after BRAF-directed therapy.
This was a single-center retrospective cohort study conducted at a tertiary care cancer center in Texas from 2017 to 2021. Fifty-seven consecutive patients with BRAF
-mutated ATC and at least 1 month of BRAF-directed therapy were included. Primary outcomes were overall survival (OS) and progression-free survival (PFS).
All patients had stage IVB (35%) or IVC (65%) ATC. Approximately 70% of patients treated with BRAF-directed therapy ultimately had surgical resection of residual disease. Patients who had neoadjuvant BRAF-directed therapy followed by surgery (
= 32) had 12-month OS of 93.6% confidence interval (CI) 84.9-100 and PFS of 84.4% CI 71.8-96.7. Patients who had surgery before BRAF-directed therapy (
= 12) had 12-month OS of 74.1% CI 48.7-99.5 and PFS of 50% CI 21.7-78.3. Finally, patients who did not receive surgery after BRAF-directed therapy (
= 13) had 12-month OS of 38.5% CI 12.1-64.9 and PFS of 15.4% CI 0-35.0. Neoadjuvant BRAF-directed therapy reduced tumor size, extent of surgery, and surgical morbidity score. Subgroup analysis suggested that any residual ATC in the surgical specimen was associated with significantly worse 12-month OS and PFS (OS = 83.3% CI 62.6-100, PFS = 61.5% CI 35.1-88) compared with patients with pathologic ATC complete response (OS = 100%, PFS = 100%).
We observed that neoadjuvant BRAF-directed therapy reduced extent of surgery and surgical morbidity. While acknowledging potential selection bias, the 12-month OS rate appeared higher in patients who had BRAF-directed therapy followed by surgery as compared with BRAF-directed therapy without surgery; yet, it was not significantly different from surgery followed by BRAF-directed therapy. PFS appeared higher in patients treated with neoadjuvant BRAF-directed therapy relative to patients in the other groups. These promising results of neoadjuvant BRAF-directed therapy followed by surgery for BRAF-mutated ATC should be confirmed in prospective clinical trials.
