Treatment of advanced thyroid cancer with axitinib: Phase 2 study with pharmacokinetic/pharmacodynamic and quality‐of‐life assessments

Locati, Laura D.; Licitra, Lisa; Agate, Laura; Ou, Sai Hong Ignatius; Boucher, Andrée; Jarząb, Barbara; Qin, Shukui; Kane, Madeleine A.; Wirth, Lori J.; Chen, Connie; Kim, Sinil; Ingrosso, Antonella; Pithavala, Yazdi K.; Bycott, Paul; Cohen, Ezra E.W.

doi:10.1002/cncr.28766

Cited by 113 publications

(58 citation statements)

References 35 publications

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“…Almost all patients experienced AEs, the most common grade 3-4 being hypertension, proteinuria, diarrhea, weight loss, and fatigue (39,40). Similar results were found in another phase II trial (41).…”

Section: Axitinibsupporting

confidence: 81%

Radioactive iodine-refractory differentiated thyroid cancer: an uncommon but challenging situation

Schmidt

Iglesias

Klain

et al. 2017

Arch. Endocrinol. Metab.

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Radioiodine (RAI)-refractory thyroid cancer is an uncommon entity, occurring with an estimated incidence of 4-5 cases/year/million people. RAI refractoriness is more frequent in older patients, in those with large metastases, in poorly differentiated thyroid cancer, and in those tumors with high 18-fluordeoxyglucose uptake on PET/CT. These patients have a 10-year survival rate of less than 10%. In recent years, new therapeutic agents with molecular targets have become available, with multikinase inhibitors (MKIs) being the most investigated drugs. Two of these compounds, sorafenib and lenvatinib, have shown significant objective response rates and have significantly improved the progression-free survival in the two largest published prospective trials on MKI use. However, no overall survival benefit has been achieved yet. This is probably related to the crossover that occurs in most patients who progress on placebo treatment to the open treatment of these studies. In consequence, the challenge is to correctly identify which patients will benefit from these treatments. It is also crucial to understand the appropriate timing to initiate MKI treatment and when to stop it. The purpose of this article is to define RAI refractoriness, to summarize which therapies are available for this condition, and to review how to select patients who are suitable for them. Arch Endocrinol Metab. 2017;61(1):81-9

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Section: Axitinibsupporting

confidence: 81%

Radioactive iodine-refractory differentiated thyroid cancer: an uncommon but challenging situation

Schmidt

Iglesias

Klain

et al. 2017

Arch. Endocrinol. Metab.

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“…With these agents, partial responses were observed (Ahmed, et al 2011;214 Bastholt, et al 2016;Bible, et al 2010;Cabanillas, et al 2017;215 Cabanillas, et al 2015;Capdevila, et al 2012;Carr, et al 2010;Cohen, et al 2008;Gupta-Abramson, et al 216 2008;Hoftijzer, et al 2009;Kloos, et al 2009;Leboulleux, et al 2012;Locati, et al 2014;Schlumberger, et 217 al. 2015;Sherman, et al 2008) and even more importantly median progression-free survival (PFS) was 218 prolonged in phase III trials when compared with placebo ( Table 2).…”

Section: Molecular-targeted Therapy 204mentioning

confidence: 99%

Treatment of refractory thyroid cancer

Berdelou¹,

Lamartina²,

Klain³

et al. 2018

Endocrine-Related Cancer

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Distant metastases from thyroid cancer of follicular origin are uncommon. Treatment includes levothyroxine administration, focal treatment modalities with surgery, external radiation therapy and thermal ablation, and radioiodine in patients with uptake of 131 I in their metastases. Two thirds of distant metastases become refractory to radioiodine at some point, and when there is a significant tumor burden and documented progression on imaging, a treatment with a kinase inhibitor may provide benefits.

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“…Most common AEs were similar-fatigue, dyspnea, diarrhea, decrease weight, pain in extremity, hypertension, decreased appetite, palmar-plantar erythrodysesthesia, hypocalcemia, and myalgia. Quality of life was maintained during treatment with axitinib without any deterioration or interference in daily life caused by symptoms (16).…”

Section: Multitargeted Kinase Inhibitorsmentioning

confidence: 97%

Lenvatinib in Advanced, Radioactive Iodine–Refractory, Differentiated Thyroid Carcinoma

Yeung¹,

Cohen²

2015

Clinical Cancer Research

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Management options are limited for patients with radioactive iodine refractory, locally advanced, or metastatic differentiated thyroid carcinoma. Prior to 2015, sorafenib, a multitargeted tyrosine kinase inhibitor, was the only approved treatment and was associated with a median progression-free survival (PFS) of 11 months and overall response rate (ORR) of 12% in a phase III trial. Lenvatinib, a multikinase inhibitor with high potency against VEGFR and FGFR demonstrated encouraging results in phase II trials. Recently, the pivotal SELECT trial provided the basis for the FDA approval of lenvatinib as a second targeted therapy for these patients. Median PFS of 18.3 months in the lenvatinib group was significantly improved from 3.6 months in the placebo group, with an HR of 0.21 (95% confidence interval, 0.4-0.31; P < 0.0001). ORR was also significantly increased in the lenvatinib arm (64.7%) compared with placebo (1.5%). In this article, we will review the molecular mechanisms of lenvatinib, the data from preclinical studies to the recent phase III clinical trial, and the biomarkers being studied to further guide patient selection and predict treatment response.

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Treatment of advanced thyroid cancer with axitinib: Phase 2 study with pharmacokinetic/pharmacodynamic and quality‐of‐life assessments

Cited by 113 publications

References 35 publications

Radioactive iodine-refractory differentiated thyroid cancer: an uncommon but challenging situation

Radioactive iodine-refractory differentiated thyroid cancer: an uncommon but challenging situation

Treatment of refractory thyroid cancer

Lenvatinib in Advanced, Radioactive Iodine–Refractory, Differentiated Thyroid Carcinoma

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