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|Ref Type||Journal Article|
|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.|
|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.|
|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 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 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 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|