A combination therapy shows clinical benefit in BRAF V600E-mutated anaplastic thyroid cancer


Anaplastic thyroid carcinomas (ATCs) are undifferentiated tumors with poor patient outcome and a highly lethal malignancy. About 1% to 10% of thyroid cancers are ATCs. 20% to 50% ATCs harbor BRAF V600E mutation. The combination therapy of the BRAF inhibitor (dabrafenib) and the MEK inhibitor (trametinib) showed robust clinical activity by dual inhibition of the MAPK signaling pathway in non-small-cell lung cancer with BRAF V600E mutation. In a phase II trial, 100 patients with BRAF V600E mutation across seven rare cancer types were treated with the dabrafenib and trametinib combination therapy. In the subgroup analysis of 16 patients with ATCs, the results revealed that the overall response rate was 69%. The median progression-free survival and overall survival were not reached at the time of data cutoff. The safety and tolerability of the combination therapy were analyzed across all patients. The safety profile was similar to previous reports in other cancer types. The data revealed that the combination therapy led to a greater clinical benefit and manageable toxicity in BRAF V600E-mutated anaplastic thyroid cancer.


Subbiah V, Kreitman RJ, Wainberg AZ, et al. J Clin Oncol, 2018 Jan 1;36(1):7-13

doi: 10.1200/JCO.2017.73.6785.

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