Combination Therapy with Sorafenib and Vemurafenib Is Effective in Anaplastic Thyroid Cancer

2016 ◽  
Vol 223 (4) ◽  
pp. S45 ◽  
Author(s):  
Jasmine Shell ◽  
Lisa Zhang ◽  
Yaqin Zhang ◽  
Min Shen ◽  
Myriem Boufraqech ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Combination Therapy ◽  
Anaplastic Thyroid Cancer

scholarly journals Salutary Response to Targeted Therapy in Anaplastic Thyroid Cancer

2019 ◽  
Vol 7 ◽  
pp. 232470961989094 ◽  
Author(s):  
Sasan Fazeli ◽  
Edina Paal ◽  
Jessica H. Maxwell ◽  
Kenneth D. Burman ◽  
Eric S. Nylen ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapy ◽  
Side Effects ◽  
Combination Therapy ◽  
Braf Inhibitor ◽  
Anaplastic Thyroid Cancer ◽  
Mek Inhibitor ◽  
Braf V600e ◽  
Aggressive Tumor ◽  
Well Differentiated

Context. Anaplastic thyroid cancer (ATC) is an aggressive tumor with a median survival of 3 to 9 months, a 1-year survival of less than 10% and without definitive therapies. Recently, in BRAF V600E mutated ATCs, new targeted therapy using a combination of a BRAF inhibitor, dabrafenib (Dab), with a mitogen-activated extracellular protein kinase (MEK) inhibitor, trametinib (Tram), has shown significant promise. Case Description. We report a case of aggressive ATC with 5 sequence mutations: BRAF V600E (mutation fraction [MF] 34%), TERT E441del (MF 37%), RET N579K (MF 55%), EZH2 D154E (MF 60%), and CDK4 S259L (MF 48%). The patient had a dramatic response to the Dab/Tram combination with near complete resolution of his lung, bone, hepatic, and splenic lesions soon after starting therapy. Unfortunately, intolerable side effects (grade 2-3) on this regimen required tapering and discontinuation of the treatment. He had a quick resurgence of disease after stopping the combination therapy. The patient died approximately 3 months after discontinuing Dab/Tram. Autopsy revealed an atrophic thyroid gland with microscopic subcapsular focus of well-differentiated papillary thyroid carcinoma. There was extensive lymphatic spread of the tumor throughout bilateral lungs with fibrosis. No other metastatic site was identified. Conclusion. We report a unique case of ATC with 2 new mutations of EZH2 D154E and CDK S529L. This case exemplifies the significant promise Dab/Tram therapy holds, the potential side effects that limit their use, and autopsy findings status post use of this combination therapy.

scholarly journals Lenvatinib Promotes the Antitumor Effects of Doxorubicin in Anaplastic Thyroid Cancer

2020 ◽  
Author(s):  
Xi Su ◽  
Jiaxin Liu ◽  
Haihong Zhang ◽  
Qingqing Gu ◽  
Xinrui Zhou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Combination Therapy ◽  
Cell Cycle Arrest ◽  
Anaplastic Thyroid Cancer ◽  
Antitumor Efficacy ◽  
Potential Candidate ◽  
Antitumor Effects ◽  
Cycle Arrest

Abstract Background Anaplastic thyroid cancer (ATC) is a kind of rare thyroid cancer with very poor prognosis. It is one of the deadliest cancers in human due to the aggressive behavior and resistance to treatment. Doxorubicin has been approved in ATC treatment as a single agent, but monotherapy still shows no improvement of the total survival in advanced ATC. Lenvatinib was investigated with encouraging results in treating the patients with radioiodine-refractory differentiated thyroid cancer (DTC). However, antitumor efficacy of combination therapy with lenvatinib and doxorubicin remains largely unclear. Methods The antitumor efficacy of combination therapy with lenvatinib and doxorubicin on ATC cell proliferation and was assessed by the MTT assay and colony formation. Flow cytometry were employed to assess ATC cells’ apoptosis and cell cycle arrest in response to combination therapy. Xenograft models were used to test its in vivo antitumor activity. Result Lenvatinib monotherapy was less effective than doxorubicin in treating ATC cell lines and xenografts model. The combination therapy of lenvatinib and doxorubicin significantly inhibited ATC cell proliferation and tumor growth in nude mice, and induced cell apoptosis and cell cycle arrest in compared to lenvatinib or doxorubicin monotherapy. Conclusion Lenvatinib promotes the antitumor effects of doxorubicin in ATC cell and xenografts model. Lenvatinib/doxorubicin combination may be a potential candidate therapeutic approach for ATC.

scholarly journals Synergistic Anticancer Activity of N-Hydroxy-7-(2-Naphthylthio) Heptanomide, Sorafenib, and Radiation Therapy in Patient-Derived Anaplastic Thyroid Cancer Models

2021 ◽  
Vol 22 (2) ◽  
pp. 536
Author(s):  
Hyeok Jun Yun ◽  
Hee Jun Kim ◽  
Jungmin Kim ◽  
Sang Yong Kim ◽  
Hang-Seok Chang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Radiation Therapy ◽  
Thyroid Cancer ◽  
Combination Therapy ◽  
Intracellular Signaling ◽  
Xenograft Model ◽  
Anaplastic Thyroid Cancer ◽  
Anticancer Effect ◽  
Mouse Xenograft Model

Anaplastic thyroid cancer (ATC) is an undifferentiated and advanced form of thyroid cancer, accompanied with a high ratio of epigenetic adjustment, which occurs more than genetic mutations. In this study, we aimed to evaluate the synergistic anticancer effect (in vitro and in vivo) of the new combination of N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA) and sorafenib with radiation therapy in pre-clinical models of ATC. The ATC cell lines, YUMC-A1 and YUMC-A2, were isolated from the current patients who were treated with HNHA and sorafenib, either as monotherapy or combination therapy. Synergistic anticancer effect of the combination therapy on the intracellular signaling pathways and cell cycle was assessed via flow cytometry and immunoblot analysis. To examine tumor shrinkage activity in vivo, an ATC cell line-derived mouse xenograft model was used. Results showed that the combination therapy of HNHA and sorafenib with radiation promoted tumor suppression via caspase cleavage and cell cycle arrest in patient-derived ATC. In addition, the combination therapy of HNHA and sorafenib with radiation was more effective against ATC than therapy with HNHA or sorafenib with radiation. Thus, the combination of HNHA and sorafenib with radiation may be used as a novel curative approach for the treatment of ATC.

204 The role of immune checkpoint inhibitor as a single agent or combination therapy in advanced thyroid cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A219-A220
Author(s):  
Ju Young Lee ◽  
Inae Park ◽  
Myungwoo Nam ◽  
Christmann Low ◽  
Eugene Kim ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Combination Therapy ◽  
Thyroid Carcinoma ◽  
Clinical Oncology ◽  
Differentiated Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Anaplastic Thyroid Cancer ◽  
Anaplastic Thyroid Carcinoma ◽  
Search Terms

BackgroundThere is a high unmet need for effective systemic treatment for patients with metastatic radioactive iodine refractory (RAI-R) differentiated thyroid cancer (DTC) and anaplastic thyroid cancer (ATC). Immunotherapy may be used as an alternative option for those without targetable mutations or have become resistant to targeted therapy. Here we review the clinical trials and retrospective studies and discuss the potential role of immune checkpoint inhibitors (ICIs) in advanced thyroid cancer.MethodsThe details of pertinent clinical trials were obtained from clinicaltrials.gov (NIH) using search terms including ‘thyroid cancer’ and ‘immunologic.’ The NCT numbers and search terms were used to search for published results on databases such as PubMed, American Association of Cancer Research, and American Society of Clinical Oncology. The efficacy outcome measures were determined using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.ResultsIn RAI-R DTC, responses to three different regimens have been reported: pembrolizumab, nivolumab plus ipilimumab, and pembrolizumab plus lenvatinib. No CR was reported, and the overall response rates (ORRs) varied from 9% (pembrolizumab monotherapy and nivolumab plus ipilimumab) to 64% (pembrolizumab plus lenvatinib) (figure 1a).1–4 In ATC, four studies have reported favorable outcomes in the context of dabrafenib and trametinib.5 The efficacy of spartalizumab, a PD1-inhibitor, was evaluated in a phase I/II trial, rendering an ORR of 19%, with 3 CRs (7%) and 5 PRs (12%) [6]. The study of nivolumab plus ipilimumab reported an ORR of 30% in ATC, with a near CR and two without clear evidence of disease at 13 and 26 months.2 A trial that tested the combination of atezolizumab, vemurafenib, and cobimetinib in BRAFV600E-mutated patients reported an ORR of 59%.7 A retrospective study reported an ORR of 60% after adding pembrolizumab at the time of progression on lenvatinib8 (figure 1b). There are 25 ongoing trials evaluating the efficacy of ICIs in different types of thyroid cancer. Three trials are testing pembrolizumab as monotherapy, three trials are assessing ICI combination therapy, and six trials are testing the efficacy of various ICI and tyrosine kinase inhibitor (TKI) combinations (figure 2).Abstract 204 Figure 1Comparison of responses in different regimens*The study population consisted only of BRAFV600E-positive patients**Retrospective studyAbbreviations: CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; Uneval; unevaluable; PEM, pembrolizumab; IPI, ipilimumab; NIVO, nivolumab; LENV, lenvatinib; ATEZO, atezolizumab; VEM, vemurafenib; COBI, cobimetinib; DAB, dabrafenib; TRAME, trametinib.Abstract 204 Figure 2comparison of responses in different regimensA. Number of checkpoint inhibition trials for various thyroid cancer histologies. B. Landscape of combination checkpoint inhibition agents.Abbreviations: DTC, differentiated thyroid cancer; ATC, anaplastic thyroid cancer, MTC, medullary thyroid cancer; NIVO, nivolumab; IPI, ipilimumab; LENV, lenvatinib; ATEZO, atezolizumab; VEM, vemurafenib; COBI, cobimetinib, DAB, dabrafenib; TRAME, trametinib; PEM, pembrolizumab; DOXY, doxycycline; SBRT: Stereotactic radiation therapy.ConclusionsThe recent trials and a retrospective study have reported favorable outcomes in ATC, suggesting ICIs have a potential role in treating patients with ATC. In particular, dual ICIs or combination of TKI and ICI can be developed as treatment options for ATC. Further large scale randomized prospective studies are required to establish ICIs as standard of care.ReferencesMehnert JM, et al. Pembrolizumab for advanced papillary or follicular thyroid cancer: preliminary results from the phase 1b KEYNOTE-028 study. Journal of Clinical Oncology 2016; 34: 6091–6091.Lorch JH, et al. A phase II study of nivolumab (N) plus ipilimumab (I) in radioidine refractory differentiated thyroid cancer (RAIR DTC) with exploratory cohorts in anaplastic (ATC) and medullary thyroid cancer (MTC). Journal of Clinical Oncology38, no. 15_suppl (May 20, 2020) 6513–6513.Haugen B, et al. Lenvatinib plus pembrolizumab combination therapy in patients with radioiodine-refractory (RAIR), progressive differentiated thyroid cancer (DTC): Results of a multicenter phase II international thyroid oncology group trial. Journal of Clinical Oncology38, no. 15_suppl (May 20, 2020) 6512–6512.Schlumberger M, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med 2015; 372:621–30.Subbiah V, et al. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer. Journal of Clinical Oncology 2018; 36:7–13.Capdevila J, et al. PD-1 Blockade in anaplastic thyroid carcinoma. Journal of Clinical Oncology38, no. 23 (August 10, 2020) 2620–2627.Cabanillas ME, et al. Atezolizumab combinations with targeted therapy for anaplastic thyroid carcinoma (ATC). Journal of Clinical Oncology 2020;38(15).Iyer PC, et al. Salvage pembrolizumab added to kinase inhibitor therapy for the treatment of anaplastic thyroid carcinoma. J Immunother Cancer 2018;6:68.

scholarly journals Lenvatinib Promotes the Antitumor Effect of Doxorubicin in Anaplastic Thyroid Cancer

2020 ◽  
Author(s):  
Xi Su ◽  
Jiaxin Liu ◽  
Haihong Zhang ◽  
Qingqing Gu ◽  
Xinrui Zhou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Combination Therapy ◽  
Cell Cycle Arrest ◽  
Antitumor Effect ◽  
Anaplastic Thyroid Cancer ◽  
Antitumor Efficacy ◽  
Potential Candidate ◽  
Cycle Arrest

Abstract Background: Anaplastic thyroid cancer (ATC) is a kind of rare thyroid cancer with very poor prognosis. It is one of the deadliest cancers in human due to the aggressive behavior and resistance to treatment. Doxorubicin has been approved in ATC treatment as a single agent, but monotherapy still shows no improvement of the total survival in advanced ATC. Lenvatinib was investigated with encouraging results in treating the patients with radioiodine-refractory differentiated thyroid cancer (DTC). However, antitumor efficacy of combination therapy with lenvatinib and doxorubicin remains largely unclear. Methods: The antitumor efficacy of combination therapy with lenvatinib and doxorubicin on ATC cell proliferation and was assessed by the MTT assay and colony formation. Flow cytometry were employed to assess ATC cells’ apoptosis and cell cycle arrest in response to combination therapy. Xenograft models were used to test its in vivo antitumor activity. Result: Lenvatinib monotherapy was less effective than doxorubicin in treating ATC cell lines and xenografts model. The combination therapy of lenvatinib and doxorubicin significantly inhibited ATC cell proliferation and tumor growth in nude mice, and induced cell apoptosis and cell cycle arrest in compared to lenvatinib or doxorubicin monotherapy. Conclusion: Lenvatinib promotes the antitumor effect of doxorubicin in ATC cell and xenografts model. Lenvatinib/doxorubicin combination may be a potential candidate therapeutic approach for anaplastic thyroid cancer.

scholarly journals Anti-cancer Activity of Paclitaxel, Lenvatinib and Radiation Combination Therapy on Anaplastic Thyroid Cancer in Vitro and in Vivo

2019 ◽  
Vol 35 (2) ◽  
pp. 19-25
Author(s):  
Shiyeol Jun ◽  
Soo Young Kim ◽  
Seok-Mo Kim ◽  
Ki Cheong Park ◽  
Hee Jun Kim ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Combination Therapy ◽  
Anaplastic Thyroid Cancer ◽  
Anti Cancer ◽  
Cancer Activity

Anaplastic thyroid cancer: a diagnostic and therapeutic challenge

2018 ◽  
Author(s):  
Alexandra Mirica ◽  
Rodica Petris ◽  
Radu Mirica ◽  
Sorin Paun ◽  
Corin Badiu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Anaplastic Thyroid Cancer ◽  
Therapeutic Challenge
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