Reference Detail

Ref Type

Journal Article

PMID

(26294908)

Authors

Schneider TC, de Wit D, Links TP, van Erp NP, van der Hoeven JJ, Gelderblom H, van Wezel T, van Eijk R, Morreau H, Guchelaar HJ, Kapiteijn E

Title

Beneficial Effects of the mTOR Inhibitor Everolimus in Patients with Advanced Medullary Thyroid Carcinoma: Subgroup Results of a Phase II Trial.

Journal	Vol	Issue	Date	Pages	Journal Short Title
International journal of endocrinology	2015		2015	348124	Int J Endocrinol

URL

Abstract Text

Objective. Until recently, advanced medullary thyroid cancer (MTC) had few treatment options except surgery. The mTOR inhibitor everolimus has shown encouraging results in neuroendocrine tumors. As part of a prospective phase II study, we analyzed the safety and efficacy of everolimus in advanced MTC. Methods. Seven patients with per RECIST 1.1 documented advanced MTC were included and received everolimus 10 mg daily. The primary objective was determining treatment efficacy. Secondary endpoints included progression-free survival (PFS), overall survival (OS), toxicity, and pharmacokinetics (PK). Results. Median follow-up duration was 28 weeks (17-147). Five patients (71%) showed SD, of which 4 (57%) showed SD >24 weeks. Median PFS and OS were 33 (95%CI: 8-56) and 30 (95%CI: 15-45) weeks, respectively. Toxicity was predominantly grade 1/2 and included mucositis (43%), fatigue (43%), and hypertriglyceridemia (43%). Four MTCs harbored the somatic RET mutation c.2753T>C, p.Met918Thr. The best clinical response was seen in a MEN2A patient. PK characteristics were consistent with phase I data. One patient exhibited extensive toxicity accompanying elevated everolimus plasma concentrations. Conclusions. This study suggests that everolimus exerts clinically relevant antitumor activity in patients with advanced MTC. Given the high level of clinical benefit and the relatively low toxicity profile, further investigation of everolimus in these patients is warranted.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
RET mutant	thyroid gland medullary carcinoma	sensitive	Everolimus	Phase II	Actionable	In a Phase II trial, Afinitor (everolimus) treatment resulted in stable disease in 71% (5/7) of medullary thyroid cancer patients, including patients harboring RET mutations, with median progression-free survival of 33 weeks (PMID: 26294908; NCT01118065).	26294908
RET C620R	thyroid gland medullary carcinoma	predicted - sensitive	Everolimus	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Afinitor (everolimus) treatment resulted in stable disease of 116 weeks in a MEN2A patient with medullary thyroid cancer harboring a RET C620R mutation (PMID: 26294908; NCT01118065).	26294908
RET M918T	thyroid gland medullary carcinoma	predicted - sensitive	Everolimus	Case Reports/Case Series	Actionable	In a Phase II clinical trial, Afinitor (everolimus) treatment resulted in stable disease in 71% (5/7) of medullary thyroid cancer patients, and 4 of the 7 patients harbored a RET M918T mutation (PMID: 26294908; NCT01118065).	26294908