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 Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Vol 28
Issue 14
Date 2010 May 10
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
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 C634Y thyroid medullary carcinoma predicted - sensitive Sorafenib Phase II 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). 20368568
RET C634F thyroid medullary carcinoma predicted - sensitive Sorafenib Phase II 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). 20368568
RET C618R thyroid medullary carcinoma predicted - sensitive Sorafenib Phase II 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). 20368568
RET C634R thyroid medullary carcinoma predicted - sensitive Sorafenib Phase II Actionable In a Phase II trial, Nexavar (sorafenib) treatment resulted in partial response in 50% (1/2) and stable disease in 50% (1/2) of patients with medullary thyroid carcinoma harboring RET C634R (PMID: 20368568). 20368568
Unknown unknown thyroid medullary carcinoma not applicable Sorafenib Phase II Actionable In a Phase II trial, Nexavar (sorafenib) treatment resulted in partial response in 6.3% (1/16) and stable disease in 87.5% (14/16) of patients with sporadic medullary thyroid carcinoma, with a median progression free survival of 17.9 months (PMID: 20368568). 20368568
RET M918T thyroid medullary carcinoma predicted - sensitive Sorafenib Phase II 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). 20368568