Neoadjuvant Tyrosine Kinase Inhibitor Therapy to Downstage Patients With Unresectable Differentiated Thyroid Cancers
Results from a retrospective review demonstrated that administration of neoadjuvant tyrosine kinase inhibitor (TKI) therapy can effectively downstage patients with unresectable differentiated thyroid cancers, allowing patients to achieve R0 resection with fewer morbidities.
“Limited treatment options exist for inoperable thyroid cancers,” stated Kylie Dickerson, MD, University of Arizona, Phoenix, Arizona, and coauthors. “We evaluated whether neoadjuvant use of systemic tyrosine kinase inhibitors facilitates surgery of differentiated thyroid cancers in this challenging context.”
In this single-institution study, researchers collected data from 42 patients with locoregionally advanced, resectable or unresectable papillary, follicular, or anaplastic thyroid carcinomas treated with neoadjuvant TKI therapy (dabrafenib plus trametinib, lenvatinib plus pembrolizumab, or lenvatinib monotherapy) using multidisciplinary protocols.
At a median follow-up of 2 years, researchers identified 9 patients treated with the intent to improve resectability of the primary or recurrent/residual tumor. Of those patients, 6 had distant metastases in the lungs (n = 6), vertebral/axial bones (n = 6), or sternum (n = 1). Tumors harbored BRAF V600E mutations (6 patients with papillary thyroid carcinoma), RAS/TERT mutations (2 patients with follicular thyroid carcinoma), or NCOA4-RET fusions.
Most patients received therapy for < 6 months with visible radiologically confirmed results within weeks of treatment initiation. All patients who underwent surgical resection achieved R0 resection without major surgical complications or aerodigestive structure resection. Therapy was well tolerated with 4 minor and 1 major toxicity that halted therapy but not surgery. Patients with distant metastases continued to receive therapy and all patients were alive without new locoregional recurrence.
“Neoadjuvant use of tyrosine kinase inhibitors seems extremely effective in downstaging surgically unresectable differentiated thyroid cancers to achieve R0 resection while avoiding unnecessary surgical morbidities,” concluded Dr Dickerson et al. “Prospective studies are urgently needed to define the potential role of neoadjuvant tyrosine kinase inhibitors in advanced thyroid cancer management.”
Source:
Dickerson K, Milas M, Metzger R, et al. Neoadjuvant systemic therapy for inoperable differentiated thyroid cancers: Impact on tumor resectability. Surgery. Published online: October 28, 2024. doi:10.1016/j.surg.2024.08.046
