An Evaluation of Clinical Efficacy of Immune Checkpoint Inhibitors for Patients with Anaplastic Thyroid Carcinoma

Hatashima, Alycia; Archambeau, Brianna; Armbruster, Heather; Xu, Menglin; Shah, Manisha H.; Konda, Bhavana; Limbach, Abberly Lott; Sukrithan, Vineeth

doi:10.1089/thy.2022.0073

Cited by 19 publications

(15 citation statements)

References 15 publications

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“…The response rate was significantly higher in patients with PD-L1-positive ATC than negative, regardless of BRAF mutation status in ATC. More recently, Hatashima et al confirmed clinical efficacy of pembrolizumab or nivolumab in a subset of patients with locally advanced and metastatic unresectable ATC [7].…”

Section: Introductionmentioning

confidence: 95%

Expression of T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains (TIGIT) in anaplastic thyroid carcinoma

et al. 2022

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Background Immune checkpoint proteins have not been fully examined in follicular cell-derived thyroid carcinoma and medullary thyroid carcinoma (MTC). Anaplastic thyroid carcinoma (ATC) is one of the most aggressive carcinomas. Even multimodal treatment does not result in favorable clinical outcomes for patients with ATC. Anti-tumor immunity has therefore been highlighted as having therapeutic promise for ATC. Methods We examined a novel immune checkpoint receptor, T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains (TIGIT), in variable thyroid lesions: adenomatous goiter, follicular adenoma, and thyroid carcinoma (TC) using immunohistochemistry (IHC). Results Our IHC results showed that TIGIT expression was detected in cancer cells of MTC and high-grade TC: poorly differentiated thyroid carcinoma (PDTC) and ATC. Neoplastic cells were positive for TIGIT in four of five MTCs (80.0%), 17 of 31 ATCs (54.8%) and in 3 of 12 PDTCs (25.0%). TIGIT was not detected in any adenomatous goiters, thyroid benign tumors, or differentiated thyroid carcinoma (DTCs). Intriguingly, ATC cells showing pleomorphic/giant cell features were positive for TIGIT, while ATC cells with other cell morphologies lacked the immunoreactivity. Intra-tumoral immune cell was inclined to be enriched in TIGI-positive ATC. Although coexisting papillary thyroid carcinoma (PTC) components demonstrated high-grade microscopic features, neither the PTC nor follicular thyroid carcinoma (FTC) components expressed TIGT in any composite ATCs. Conclusion TIGIT was immunohistochemically found in MTC with high frequency and partially in high-grade TC. TIGIT expression in cancer cells may be beneficial for a potential utility in MTC and a subset of high-grade TC, especially ATC therapy.

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Section: Introductionmentioning

confidence: 95%

Expression of T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains (TIGIT) in anaplastic thyroid carcinoma

et al. 2022

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“…Four studies evaluating immunotherapy alone have been published in thyroid cancers [ 12 , 20 , 65 , 66 ]. Considering the preclinical rationale of ICI in TCAs, three of them included TCAs [ 12 , 20 , 65 ]. In Table 1 , the results of these clinical studies are summarized.…”

Section: Clinical Evidencementioning

confidence: 99%

“…Concerning pembrolizumab, Hatashima et al recently published a retrospective case series of 13 patients with locally advanced or metastatic unresectable ATC who received immune checkpoint inhibitor therapy (pembrolizumab or nivolumab) at a single institution [ 12 ]. In this study, the objective response rate was 16%.…”

Section: Clinical Evidencementioning

confidence: 99%

“…Median OS was 4.4 months and one-year survival rate 38%. Among patients with a clinical benefit, after a median follow-up of 13.5 months, median OS had not been reached with a patient alive after 29 months [ 12 ]. Concerning safety, 46% of patients experienced immune-related adverse events in this study.…”

Section: Clinical Evidencementioning

confidence: 99%

“…The response to pembrolizumab immunotherapy is associated with the elevated expression of programmed death-ligand 1 (PD-L1) or high tumor mutational burden (TMB) [ 9 , 10 , 11 ]. In ATC associated with high PD-L1/TMB, the effect of immune checkpoint inhibitors is still low, with 1.9 months of median progression-free survival and 4.4 months of median overall survival (OS) [ 12 ]. Rapid tumor development is incompatible with a low response rate and/or a long time to response [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Rationale Efficacy and Safety Evidence of Lenvatinib and Pembrolizumab Association in Anaplastic Thyroid Carcinoma

et al. 2022

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Anaplastic thyroid carcinoma (ATC) are highly aggressive malignant tumors with poor overall prognosis despite multimodal therapy. As ATC are extremely rare, no randomized controlled study has been published for metastatic disease. Thyrosine kinase inhibitors, especially lenvatinib and immune checkpoint inhibitors such as pembrolizumab, are emerging drugs for ATC. Few studies have reported the efficacity of pembrolizumab and lenvatinib association, resulting in its frequent off-label use. In this review, we discuss rationale efficacy and safety evidence for the association of lenvatinib and pembrolizumab in ATC. First, we discuss preclinical rationale for pembrolizumab monotherapy, lenvatinib monotherapy and synergistic action of pembrolizumab and lenvatinib in the metastatic setting. We also discuss clinical evidence for immunotherapy and pembrolizumab in ATC through the analysis of studies evaluating immunotherapy, lenvatinib and pembrolizumab lenvatinib association in ATC. In addition, we discuss the safety of this association and potential predictive biomarkers of efficiency.

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Initial Management of BRAF V600E-Variant Anaplastic Thyroid Cancer

Hamidi,

Dadu,

Zafereo

et al. 2024

JAMA Oncol

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ImportanceBRAF/MEK inhibitors revolutionized the treatment of BRAF V600E-variant anaplastic thyroid carcinoma (BRAFv-ATC), offering improved outcomes for patients with this previously incurable disease.ObservationsAnaplastic thyroid carcinoma (ATC) accounts for approximately half of thyroid cancer−related deaths. It presents as a rapidly growing tumor that often invades locoregional structures and spreads to distant sites early; therefore, prompt diagnosis, staging, and treatment initiation are of the essence in the treatment of ATC. Although most oncologists will encounter a patient with ATC in their practice, the rarity of this disease makes treatment challenging, particularly because those with BRAFv-ATC no longer have a dismal prognosis. BRAF/MEK kinase inhibitors have transformed the outlook and treatment of BRAFv-ATC. Therefore, molecular profiling to identify these patients is critical. More recently, the addition of immunotherapy to BRAF/MEK inhibitors as well as the use of the neoadjuvant approach were shown to further improve survival outcomes in BRAFv-ATC. Many of these recent advances have not yet been incorporated in the currently available guidelines, allowing for disparities in the treatment of patients with BRAFv-ATC across the US. With the increasing complexity in the management of BRAFv-ATC, this Consensus Statement aims to formulate guiding recommendations from a group of experts to facilitate therapeutic decision-making.Conclusions and RelevanceThis Consensus Statement from the FAST (Facilitating Anaplastic Thyroid Cancer Specialized Treatment) group at MD Anderson Cancer Center emphasizes that rapid identification of a BRAF V600E pathogenic variant and timely initiation of sequential therapy are critical to avoid excess morbidity and mortality in patients with BRAFv-ATC. In the past decade, remarkable progress has been made in the treatment of patients with BRAFv-ATC, justifying these new evidence-based recommendations reached through a consensus of experts from a high-volume center.

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An Evaluation of Clinical Efficacy of Immune Checkpoint Inhibitors for Patients with Anaplastic Thyroid Carcinoma

Cited by 19 publications

References 15 publications

Expression of T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains (TIGIT) in anaplastic thyroid carcinoma

Expression of T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains (TIGIT) in anaplastic thyroid carcinoma

Rationale Efficacy and Safety Evidence of Lenvatinib and Pembrolizumab Association in Anaplastic Thyroid Carcinoma

Initial Management of BRAF V600E-Variant Anaplastic Thyroid Cancer

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