Reference Detail

Ref Type

Journal Article

PMID

(20368568)

Authors

Lam ET, Ringel MD, Kloos RT, Prior TW, Knopp MV, Liang J, Sammet S, Hall NC, Wakely PE, Vasko VV, Saji M, Snyder PJ, Wei L, Arbogast D, Collamore M, Wright JJ, Moley JF, Villalona-Calero MA, Shah MH

Title

Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of clinical oncology : official journal of the American Society of Clinical Oncology	28	14	2010 May 10	2323-30	J Clin Oncol

URL

Abstract Text

Mutations in the RET proto-oncogene and vascular endothelial growth factor receptor (VEGFR) activity are critical in the pathogenesis of medullary thyroid cancer (MTC). Sorafenib, a multikinase inhibitor targeting Ret and VEGFR, showed antitumor activity in preclinical studies of MTC.In this phase II trial of sorafenib in patients with advanced MTC, the primary end point was objective response. Secondary end points included toxicity assessment and response correlation with tumor markers, functional imaging, and RET mutations. Using a two-stage design, 16 or 25 patients were to be enrolled onto arms A (hereditary) and B (sporadic). Patients received sorafenib 400 mg orally twice daily.Of 16 patients treated in arm B, one achieved partial response (PR; 6.3%; 95% CI, 0.2% to 30.2%), 14 had stable disease (SD; 87.5%; 95% CI, 61.7% to 99.5%), and one was nonevaluable. In a post hoc analysis of 10 arm B patients with progressive disease (PD) before study, one patient had PR of 21+ months, four patients had SD >or= 15 months, four patients had SD <or= 6 months, and one patient had clinical PD. Median progression-free survival was 17.9 months. Arm A was prematurely terminated because of slow accrual. Common adverse events (AEs) included diarrhea, hand-foot-skin reaction, rash, and hypertension. Although serious AEs were rare, one death was seen. Tumor markers decreased in the majority of patients, and RET mutations were detected in 10 of 12 sporadic MTCs analyzed.Sorafenib is reasonably well tolerated, with suggestion of clinical benefit for patients with sporadic MTC. Caution should be taken because of the rare but fatal toxicity potentially associated with sorafenib.

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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 C618R	thyroid gland medullary carcinoma	predicted - sensitive	Sorafenib	Case Reports/Case Series	Actionable	In a Phase II trial, Nexavar (sorafenib) treatment resulted in stable disease in one patient with medullary thyroid carcinoma harboring RET C618R (PMID: 20368568; NCT00390325).	20368568
RET C634F	thyroid gland medullary carcinoma	predicted - sensitive	Sorafenib	Case Reports/Case Series	Actionable	In a Phase II trial, Nexavar (sorafenib) treatment resulted in stable disease in one patient with medullary thyroid carcinoma harboring RET C634F (PMID: 20368568; NCT00390325).	20368568
RET C634Y	thyroid gland medullary carcinoma	predicted - sensitive	Sorafenib	Case Reports/Case Series	Actionable	In a Phase II trial, Nexavar (sorafenib) treatment resulted in stable disease in one patient with medullary thyroid carcinoma harboring RET C634Y (PMID: 20368568; NCT00390325).	20368568
RET M918T	thyroid gland medullary carcinoma	predicted - sensitive	Sorafenib	Case Reports/Case Series	Actionable	In a Phase II trial, Nexavar (sorafenib) treatment resulted in partial response in 10% (1/10) and stable disease in 90% (9/10) of patients with medullary thyroid carcinoma harboring RET M918T (PMID: 20368568; NCT00390325).	20368568
RET C634R	thyroid gland medullary carcinoma	predicted - sensitive	Sorafenib	Case Reports/Case Series	Actionable	In a Phase II trial, Nexavar (sorafenib) treatment resulted in a partial response in 1 and stable disease in another patient with medullary thyroid carcinoma harboring RET C634R (PMID: 20368568; NCT00390325).	20368568