title: Beneficial Effects of the mTOR Inhibitor Everolimus in Patients with Advanced Medullary Thyroid Carcinoma: Subgroup Results of a Phase II Trial.
abstract: 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.
authors: Department of Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands ; Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.
authors: T C
authors: TC
authors: Schneider
authors: Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.
authors: D
authors: D
authors: de Wit
authors: Department of Endocrinology, University Medical Center Groningen, 9700 RB Groningen, Netherlands.
authors: T P
authors: TP
authors: Links
authors: Department of Clinical Pharmacy, Radboud University Nijmegen Medical Center, 6525 GA Nijmegen, Netherlands.
authors: N P
authors: NP
authors: van Erp
authors: Department of Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.
authors: J J M
authors: JJ
authors: van der Hoeven
authors: Department of Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.
authors: H
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authors: Gelderblom
authors: Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.
authors: T
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authors: van Wezel
authors: Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.
authors: R
authors: R
authors: van Eijk
authors: Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.
authors: H
authors: H
authors: Morreau
authors: Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.
authors: H J
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authors: Guchelaar
authors: Department of Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.
authors: E
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authors: Kapiteijn