Everolimus in anaplastic thyroid cancer: A case series.

Abstract

Background: Anaplastic thyroid cancer (ATC) is a very aggressive disease and accounts for over 50% of thyroid-cancer related deaths. mTOR inhibition has shown antitumor activity in ATC. We report our experience treating patients with ATC with everolimus off-protocol.Methods: Patients with confirmed ATC and treated with everolimus at DFCI were identified and reviewed retrospectively. NexGen sequencing was performed, and radiologic responses were correlated with mutational profile.Results: Five patients were treated from 2013 to 2016. Three patients had a response, which included one patient who achieved a partial response for 27.9 months, and two patients who had stable disease for 3.7 and 5.9 months, respectively. Genomic analysis was available in two patients and revealed that the partial responder had mutations involving the PI3K/mTOR pathway. Conclusion:Everolimus has anti-tumor activity in ATC, and responses may correlate with mutations involving the PI3K/mTOR pathway. Further studies are warranted.

PD‑L1 expression and immune cells in anaplastic carcinoma and poorly differentiated carcinoma of the human thyroid gland: A retrospective study

“…Lenvatinib has demonstrated an acceptable safety profile for Japanese patients with unresectable thyroid tumors including ATC, regardless of mutational status (15). Other therapeutic options could include everolimus when somatic mutations have been detected in the PI3K/mTOR pathway (16,17), imatinib when overexpression of PDGF receptors are detected in advanced ATC (18), and immune checkpoint inhibitor (ICI) drugs targeting PD-1 or PD-L1 (6,19).…”

Thyroid and COVID-19: a review on pathophysiological, clinical and organizational aspects

“…Target therapies, including multikinase inhibitors and mammalian target of rapamycin inhibitors, have a role in treating advanced thyroid cancers [95][96][97][98][99][100]. Some kinase inhibitors, including sorafenib, sunitinib, and vandetanib, were used against other viral agents, including coronaviruses, and their efficacy as therapeutic instruments in COVID-19 are currently under investigation [101].…”

Molecular Markers Guiding Thyroid Cancer Management

“…Recently, the BRAF inhibitor Dabrafenib and the MEK inhibitor Trametinib was also approved for treatment in ATC, in patients not responding to locoregional treatment options [ 191 ]. Today there are several other available targeted TKIs; NTRK inhibitor Larotrectinib [ 192 ], mTOR inhibitor Everolimus [ 193 ], ALK inhibitor Crizotinib [ 194 ] and the RET inhibitor Selpercatinib was recently clinically approved for RAIRD metastatic advanced TC with RET-fusion genes [ 195 , 196 ]…”

“…In our experience, patients with BRAF V600E WT ATC have responded to Lenvatinib as shown in our case report ( Box 1 ) and achieved remarkable responses allowing some ATCs to be down staged and proceed to surgery to achieve local control and effective palliation ( Box 1 , Figure 3 ). In addition, the availability of targeted therapies for rarer drivers such as NTRK inhibition with Larotrectinib [ 192 ], mTOR inhibition with Everolimus [ 193 ], ALK inhibition with Crizotinib [ 194 ] and the RET inhibition with Selpercatinib mean it is important to assess patients tumours with advanced disease for the genetic driver mutation.…”