Mutation based approaches to the treatment of anaplastic thyroid cancer.

OBJECTIVE: The treatment of anaplastic thyroid cancer (ATC) has continued to rapidly evolve over time. Increased utilization of novel, personalized therapies based upon the tumour's somatic mutation status has recently been integrated. The aim of this case series is to describe a series of patients that underwent rapid genomic testing upon their diagnosis of ATC, allowing for the early integration of novel therapies. DESIGN: A fast track pathway for genomic tumour analysis of patients with ATC was implemented at a single academic cancer hospital in January of 2020. PATIENTS: All patients were evaluated by head and neck surgery, endocrinology, and medical oncology upon diagnosis of ATC. MEASUREMENTS: Genetic work-up was completed, which prompted a recommendation for dual BRAF/MEK inhibition with dabrafenib and trametinib for tumours with BRAF V600E mutation. For patients whose tumours were BRAF V600E wild-type, pembrolizumab with lenvatinib was offered. RESULTS: A total of four patients were included in this series. Two patients (50%) had tumours that were BRAF V600E positive. Among patients that were BRAF V600E positive, both patients initiated urgent dabrafenib and trametinib dual tyrosine kinase inhibitor (TKI) therapy; with one patient demonstrating near-complete clinical response allowing for posttreatment surgery, while the other demonstrated decreased tumour burden. Among patients who were BRAF V600E wild-type, lenvatinib and pembrolizumab were recommended off-label; one patient demonstrated decreased tumour burden, but developed severe pure red cell aplasia, while the other patient is demonstrating an early clinical response. CONCLUSIONS: The integration of early genomic analysis and personalized neoadjuvant TKI therapy into the treatment of ATC can greatly benefit patient care outcomes and optimize tumour control.