Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer (DTC) and refractory medullary thyroid cancer (MTC)

Capdevila, Jaume; Trigo, José; Aller, Javier; Manzano, José Luís; Adrián, Silvia García; Llopis, Carles Zafón; Reig, Òscar; Bohn, Uriel; Cajal, Teresa Ramón y; Póveda, Manuel Durán; Astorga, Beatriz Gonzalez; López-Alfonso, Ana; Martínez, J.; Porras, Ignacio; Reina, Juan José; Palacios, Nuria; Grande, Enrique; Cillán, Elena; Matos, Ignacio; Grau, Juan J.

doi:10.1530/eje-17-0243

Cited by 36 publications

(20 citation statements)

References 23 publications

(28 reference statements)

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“…Axitinib-related AEs (neuropathy, dyspnea, proteinuria, lower leg ulceration, myocardial infarction, or cerebral ischemia/respiratory insufficiency (n56; 12%) post-hoc landmark analysis demonstrated that patients who developed diastolic BP > 90 mmHg during axitinib treatment had longer median PFS and OS compared with those who had diastolic BP < 90 mmHg. The small sample size and lack of a control group and the minimal change from baseline QoL may limit the applicability of results from the current trial 49 .…”

Section: Differentiated Thyroid Cancermentioning

confidence: 97%

“…The primary treatment of hereditary or sporadic MTC is total thyroidectomy with dissection of ipsilateral and central lymph nodes, extended in some cases to contralateral dissection, serum calcitonin level is not detectable in > 60% of patients without lymph node involvement, as opposed to < 20% of patients with lymph node involvement. When the regional metastases recurrence systemic disease localized in the neck or mediastinum, a new surgery can be performed; however, some patients with distant metastases may survive for several years or rapidly progress and die of their disease 49 . External beam radiotherapy (EBRT), other non-surgical therapies should be considered to achieve local tumor control and systemic medical therapy how first-line treatments approved for medullary thyroid cancer (MTC) 3,35 based on treating tumor-associated deleterious events [44][45][46] .…”

Section: Medullary Thyroid Carcinoma (Mtc)mentioning

confidence: 99%

“…Median PFS was 12.7 (95% CI: 10.9-34.7) and median OS was 34.7 (95% CI: 18.3 to not reached) months; one estimated OS at 12 months was 80% (95% CI: 65-97%). Notable serious AEs included Grade 1 thrombotic thrombocytopenic purpura (n = 1), Grade 2 deep venous thrombosis (n = 1), Grade 4 perianal hidradenitis suppurativa (n = 1), and Grade 3 AEs (n = 6) comprising left ventricular systolic dysfunction, asymptomatic increased lipase, osteonecrosis of the jaw, decubitus ulcer, pneumonia, and meningitis (one of each events) [49][50][51] .…”

Section: Differentiated Thyroid Cancermentioning

confidence: 99%

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Perspectives on the use of tyrosine kinase inhibitors in thyroid cancer

Quintana-Quintana¹,

Orta-Cortes²,

Tletlepantzin-Apartado³

et al. 2020

GAMO

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Introduction: Thyroid cancer has generally a good prognosis after surgical and/or radioactive iodine (RAI) treatment; however, these tumors that persist or that are not candidate to these treatments have a worse prognosis, which makes the use of tyrosine kinase inhibitors (TKIs) a good management alternative, since it has demonstrated progression-free survival (PFS) and response rate benefits, and it is, therefore, important to describe new markers and future therapies for this type of tumors. Materials and methods: The purpose of this review is to describe the current state of the treatment of advanced or relapsing thyroid cancer that is not susceptible to management with surgery or RAI, the benefits, and limitations of the use of TKIs, as well as an analysis of this tumor's molecular biology and its clinical repercussion. Results: The use of sorafenib and lenvatinib in differentiated thyroid carcinoma that is refractory to RAI, and cabozantinib and vandetanib for advanced medullary carcinomas, has demonstrated benefit in this type of patients, with an impact on PFS, response rates, and disease control. There are ongoing studies with immunotherapy, and we will be alert for their results. Conclusion: The treatment with TKI in metastatic thyroid cancer, has shown benefit, the determination of mutations and markers will determine which is the best TKI for the different subtypes of thyroid cancer.

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Section: Differentiated Thyroid Cancermentioning

confidence: 97%

Section: Medullary Thyroid Carcinoma (Mtc)mentioning

confidence: 99%

Section: Differentiated Thyroid Cancermentioning

confidence: 99%

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Perspectives on the use of tyrosine kinase inhibitors in thyroid cancer

Quintana-Quintana¹,

Orta-Cortes²,

Tletlepantzin-Apartado³

et al. 2020

GAMO

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“…Nevertheless, the study was limited by the inclusion of patients with heterogeneous disease aggressiveness, as the evidence of radiological progression was not required before entry. By contrast, a recent contribution presented at the American Society of Clinical Oncology (ASCO) 2014 meeting has assessed the activity of axitinib in 32 iodine-refractory DTC patients having documented disease progression [70]. Authors reported objective tumour response in 41% of subjects, thus suggesting a meaningful role for axitinib in this clinical setting.…”

Section: Compoundmentioning

confidence: 98%

The evolving field of kinase inhibitors in thyroid cancer

Marotta¹,

Sciammarella²,

Vitale

et al. 2015

Critical Reviews in Oncology/Hematology

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Most of the genetic events implicated in the pathogenesis of thyroid cancer (TC) involve genes with kinase activity. Thus, kinase inhibitors (KIs) are very relevant in this field. KIs are considered the most suitable treatment for patients with iodine-refractory differentiated TC; these patients comprise the subgroup with the poorer prognosis. To date, only sorafenib has been approved for this indication, but promising results have been reported with several other KIs. In particular, lenvatinib has demonstrated excellent efficacy, with both progression-free survival and objective tumour response being better than with sorafenib. Despite being considered to be well tolerated, both sorafenib and lenvatinib have shown a remarkable toxicity, which has led to dose reductions in the majority of patients and to treatment discontinuation in a significant proportion of cases. The role of KIs in differentiated TC may be revolutionised by the finding that selumetinib may restore a clinical response to radioactive iodine (RAI). Vandetanib and cabozantinib have been approved for the treatment of advanced, progressive medullary TC (MTC). Nevertheless, the toxicity of both compounds suggests their selective use in those patients with strong disease progression. Treatment with the mTOR-inhibitor everolimus, alone or in combination with somatostatin analogues, should be studied in metastatic MTC patients with slow progression of disease, these representing the vast majority of patients. KIs did not significantly impact on the clinical features of anaplastic TC (ATC).

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“…Based on published phase 2 trials, other orally available multikinase inhibitors such as sunitinib, axitinib, cabozantinib or pazopanib may produce some clinical benefit in this setting but only the results of the phase III study with vandetanib are expected in the near future. 11,13 In addition, drug-related side effects are common and could reduce patients' quality of life and increase the risk of drug-related deaths. The most important one is patient's selection as no biological or genetic biomarker has been yet elucidated to predict tumor response or patient's outcome.…”

Section: Introductionmentioning

confidence: 99%

Spanish consensus for the management of patients with advanced radioactive iodine refractory differentiated thyroid cancer

Riesco‐Eizaguirre

Galofré

Grande

et al. 2016

Endocrinología y Nutrición (English Edition)

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Background: Approximately one third of the patients with differentiated thyroid cancer (DTC) who develop structurally-evident metastatic disease are refractory to radioactive iodine (RAI). Most deaths from thyroid cancer occur in these patients. The main objective of this consensus is to address the most controversial aspects of management of these patients. Methods: On behalf of the Spanish Society of Endocrinology & Nutrition (SEEN) and the Spanish Group for Orphan and Infrequent Tumors (GETHI), the Spanish Task Force for Thyroid Cancer, consisting of endocrinologists and oncologists, reviewed the relevant literature and prepared a series of clinically relevant questions related to management of advanced RAI-refractory DTC. Results: Ten clinically relevant questions were identified by the task force. In answering to these 10 questions, the task force included recommendations regarding the best definition of refractoriness; the best therapeutic options including watchful waiting, local therapies, and systemic therapy (e.g. kinase inhibitors), when sodium iodide symporter (NIS) restoration may be expected; and how recent advances in molecular biology have increased our understanding of the disease.G. Riesco-Eizaguirre et al. Conclusions:In response to our appointment as a task force by the SEEN and GHETI, we developed a consensus to help in clinical management of patients with advanced RAI-refractory DTC. We think that this consensus will provide helpful and current recommendations that will help patients with this disorder to get optimal medical care.Cáncer diferenciado de tiroides; Refractario al yodo radioactivo; Consenso español; Manejo clínico Consenso español sobre el tratamiento de los pacientes con cáncer de tiroides diferenciado avanzado resistente al yodo radiactivo Resumen Antecedentes: Alrededor de un tercio de los pacientes con cáncer diferenciado de tiroides (CDT) que desarrollan enfermedad metastásica estructural son refractarios al yodo radiactivo. Desafortunadamente, la mayoría de las muertes debidas al cáncer de tiroides ocurren en pacientes con CDT avanzado refractario al yodo radiactivo. El principal objetivo de este consenso es abordar los aspectos más controvertidos del manejo de estos pacientes. Métodos: En nombre de la Sociedad Española de Endocrinología y Nutrición (SEEN) y del Grupo Español de Tumores Raros e Infrecuentes (GETHI), el grupo de trabajo para el Cáncer de Tiroides, compuesto por endocrinólogos y oncólogos, revisó la literatura más destacada y desarrolló una serie de preguntas clínicamente relevantes concernientes al manejo de los pacientes con CDT refractario. Resultados: Diez preguntas clínicamente relevantes fueron identificadas por el grupo de trabajo. En las respuestas el grupo incluyó recomendaciones sobre la mejor definición de la refractariedad, las mejores opciones terapéuticas, entre las cuales se incluyen la actitud expectante, las terapias locales y la terapia sistémica (por ejemplo inhibidores de tirosín-cinasa), cuándo esperar la recaptación de yodo radiactivo m...

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Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer (DTC) and refractory medullary thyroid cancer (MTC)

Cited by 36 publications

References 23 publications

Perspectives on the use of tyrosine kinase inhibitors in thyroid cancer

Perspectives on the use of tyrosine kinase inhibitors in thyroid cancer

The evolving field of kinase inhibitors in thyroid cancer

Spanish consensus for the management of patients with advanced radioactive iodine refractory differentiated thyroid cancer

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