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 anti-tumor 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.

Perspectives on the Treatment of Advanced Thyroid Cancer: Approved Therapies, Resistance Mechanisms, and Future Directions

“…Additionally, in a case series of five patients with ATC treated with everolimus 10mg daily, mOS was 7.4 months. One patient had a durable response that lasted 27.9 months, and two others had SD for 3.7 and 5.9 months, respectively ( 28 ).…”

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] While many trials of TKIs were mutation agnostic it is possible identification of the driver mutation could improve response of advanced TC with TKIs. The advances of hybridisation capture-based NGS panels, Memorial Sloan Kettering integrated mutation profiling of actionable cancer targets (MSK-IMPACT), and Foundation One, which can detect somatic and germline mutations, are becoming more accessible for clinicians to customise treatment for patients with advanced TC [197,198].…”

“…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] A man in his 60s presented to our clinic with one-month history of rapidly enlarging right neck mass and voice change. He had a family history of thyroid cancer.…”

“…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.…”

Activation of the IGF Axis in Thyroid Cancer: Implications for Tumorigenesis and Treatment

“…This mTOR inhibitor generated contrasting results when employed on thyroid tumors as efficacy was mostly dependent on tumor type and stage. Indeed, while low response rates were reported in patients with locally advanced or metastatic thyroid cancer [77], everolimus displayed antitumor activity in patients with advanced FTC [80] or MTC [78] and induced disease stability in an ATC case series [75]. Finally, the combination of everolimus and cisplatin [76] or sorafenib [79] showed clinical efficacy both in DTCs and MTCs.…”