Update on the Treatment of Medullary Thyroid Carcinoma in Patients
                    with Multiple Endocrine Neoplasia Type 2

Ilanchezhian, Maran; Khan, Samina; Okafor, Charles O.; Glod, John; Rivero, Jaydira Del

doi:10.1055/a-1145-8479

Cited by 9 publications

(9 citation statements)

References 88 publications

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“…It is important to stress that all these studies of TKIs have provided us with abundant experience for better management of side effects aiming at improved quality of life; it is likely that this initial experience with the use of these drugs and their side effects will help us acknowledge their potential and improve the management of progressive MTC, by recognizing possible predictive factors of better response. In parallel, next-generation selective TKIs are being developed with the hope for an improved outcome and fewer AEs [4, 46].…”

Section: Discussionmentioning

confidence: 99%

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Benefits and Limitations of TKIs in Patients with Medullary Thyroid Cancer: A Systematic Review and Meta-Analysis

et al. 2020

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Introduction: Tyrosine kinase inhibitors (TKIs) have been used in patients with advanced medullary thyroid carcinoma (MTC); however, data on their effectiveness and safety are limited. The aim of this systematic review and meta-analysis was to document clinical response and toxicities of TKIs in advanced MTC. Methods: We systematically searched major databases for articles or abstracts on TKI use in MTC patients until May 2018. Objective response (OR), defined as the sum of complete + partial response, expressed as percentage, was our primary endpoint, while disease stability, disease progression (DP), median progression-free survival (PFS), and drug discontinuation rate due to adverse events (AEs) were secondary endpoints. Pooled percentages, PFS time, and 95% CIs were reported. Results: Thirty-three publications were finally included in the analysis: 1 phase IV, 2 phase III trials evaluating vandetanib and cabozantinib, respectively, 20 phase I or II studies, and the remaining 10 studies of retrospective-observational nature. OR was documented in 28.6% (95% CI 25.9–31.9) of patients. Stable disease was recorded in 46.2% (95% CI 43.3–49.1). Overall, DP was observed in 22.9% (95% CI 20.4–27.6). Grade 3 or more AEs occurred in 48.5% (95% CI 45.5–51.5) of patients, and drug discontinuation was reported in 44.7% (95% CI 41.7–47.6). In general, use of TKIs conferred a PFS of 23.3 months (95% CI 21.07–25.5). In particular, vandetanib induced an OR in 33.8% (95% CI 29.6–38.0) of patients and cabozantinib in 27.7% (95% CI 22.05–33.4). DP occurred in 23.7% (95% CI 19.9–27.6) with vandetanib use and in 22.6% (95% CI 17.4–27.9) in cabozantinib-treated patients. Sorafenib, the third most frequently studied drug, showed intermediate efficacy, but higher discontinuation rates. Conclusion: Treatment with TKIs in MTC patients with progressive disease is associated with a moderate therapeutic benefit, with achievement of either disease stability or partial response in 73%. The toxicity of these drugs is not negligible, but it is, nonetheless, manageable.

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Section: Discussionmentioning

confidence: 99%

“…The disease is sporadic in 70–80% of cases and hereditary in 20–30% [2, 4]. RET (rearranged during transfection) proto-oncogene mutations play a key role in the pathogenesis of the disease.…”

Section: Introductionmentioning

confidence: 99%

Benefits and Limitations of TKIs in Patients with Medullary Thyroid Cancer: A Systematic Review and Meta-Analysis

et al. 2020

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“…TKIs veve been shown to be effective in treating patients with advanced or metastatic MTC. Two TKIs, vandetanib and cabozantinib, have been approved to treat advanced cases until now 26 . As vandetanib and cabozantinib are not universally available in all countries, another TKI, sorafenib, is offered as an alternative in the MTC.…”

Section: Discussionmentioning

confidence: 99%

Clinic Heterogeneity and Management of Pediatric Patients With Germline RET Proto-oncogene Mutation: Single-center Experience

Şıklar¹,

Kontbay²,

Dinçaslan

et al. 2023

Journal of Pediatric Hematology/Oncology

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Inherited forms of medullary thyroid carcinoma (MTC) can cause serious problems in diagnosis and follow-up. Family screening is performed, and prophylactic thyroidectomy at an appropriate age can be life-saving. This study aimed to investigate the diagnostic, clinical, laboratory characteristics, and treatment methods of cases with rearranged during transfection (RET) mutation in the childhood age group. Patients diagnosed with hereditary MTC and patients who were evaluated by detecting MTC and/or RET mutations in their families were included in this study. Nine cases from 6 families were included in the study. Seven patients were evaluated as a result of screening, whereas 2 patients, one of whom was MEN2B, were symptomatic. Prophylactic thyroidectomy was performed in 7 cases. Medullary microcarcinoma was found in all, and additional papillary thyroid carcinoma in one. An inoperable tumor was detected in one patient, and sorafenib treatment was applied. A very heterogeneous clinical presentation can be seen in a group of pediatric patients with RET mutation. In rare RET mutations, the genotype-phenotype relationship is still unclear, and different clinical pictures can be seen. Although prophylactic thyroidectomy is life-saving, it can cause iatrogenic hypothyroidism and hypoparathyroidism. Concomitant papillary microcarcinomas may occur in very young children with germline RET mutation.

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“…In addition, RET-specific TKIs in development are Selpercatinib (previously LOXO-292) and Blue-667 with more specific RET-targeting activity. These agents have demonstrated evidence of efficacy in early trial results (29,30); however, further treatments are warranted with less toxicity.…”

Section: Discussionmentioning

confidence: 99%

A Case Report of Sequential Use of a Yeast-CEA Therapeutic Cancer Vaccine and Anti-PD-L1 Inhibitor in Metastatic Medullary Thyroid Cancer

et al. 2020

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Medullary thyroid cancer (MTC) accounts for ∼4% of all thyroid malignancies. MTC derives from the neural crest and secretes calcitonin (CTN) and carcinoembryonic antigen (CEA). Unlike differentiated thyroid cancer, MTC does not uptake iodine and I-131 RAI (radioactive iodine) treatment is ineffective. Patients with metastatic disease are candidates for FDA-approved agents with either vandetanib or cabozantinib; however, adverse effects limit their use. There are ongoing trials exploring the role of less toxic immunotherapies in patients with MTC. We present a 61-year-old male with the diagnosis of MTC and persistent local recurrence despite multiple surgeries. He was started on sunitinib, but ultimately its use was limited by toxicity. He then presented to the National Cancer Institute (NCI) and was enrolled on a clinical trial with heat-killed yeast-CEA vaccine (NCT01856920) and his calcitonin doubling time improved in 3 months. He then came off vaccine for elective surgery. After surgery, his calcitonin was rising and he enrolled on a phase I trial of avelumab, a programmed death-ligand 1 (PD-L1) inhibitor (NCT01772004). Thereafter, his calcitonin decreased > 40% on 5 consecutive evaluations. His tumor was subsequently found to express PD-L1. CEA-specific T cells were increased following vaccination, and a number of potential immune-enhancing changes were noted in the peripheral immunome over the course of sequential immunotherapy treatment. Although calcitonin declines do not always directly correlate with clinical responses, this response is noteworthy and highlights the potential for immunotherapy or sequential immunotherapy in metastatic or unresectable MTC.

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Update on the Treatment of Medullary Thyroid Carcinoma in Patients with Multiple Endocrine Neoplasia Type 2

Cited by 9 publications

References 88 publications

Benefits and Limitations of TKIs in Patients with Medullary Thyroid Cancer: A Systematic Review and Meta-Analysis

Benefits and Limitations of TKIs in Patients with Medullary Thyroid Cancer: A Systematic Review and Meta-Analysis

Clinic Heterogeneity and Management of Pediatric Patients With Germline RET Proto-oncogene Mutation: Single-center Experience

A Case Report of Sequential Use of a Yeast-CEA Therapeutic Cancer Vaccine and Anti-PD-L1 Inhibitor in Metastatic Medullary Thyroid Cancer

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