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Ref Type Journal Article
PMID (23489023)
Authors Kim KB, Cabanillas ME, Lazar AJ, Williams MD, Sanders DL, Ilagan JL, Nolop K, Lee RJ, Sherman SI
Title Clinical responses to vemurafenib in patients with metastatic papillary thyroid cancer harboring BRAF(V600E) mutation.
Journal Thyroid : official journal of the American Thyroid Association
Vol 23
Issue 10
Date 2013 Oct
URL
Abstract Text Clinical benefit from cytotoxic chemotherapy for metastatic papillary thyroid carcinoma (PTC) is disappointing, and effective therapeutic approaches for these patients are urgently needed. Because kinase-activating mutations in the BRAF proto-oncogene commonly occur in advanced PTC, and inhibition of BRAF(V600E) has shown promising clinical activity in melanoma, BRAF inhibitor therapy may be an effective strategy to treat metastatic PTC.The dose escalation portion of a first-in-human, phase I study of vemurafenib, a selective RAF inhibitor, included three patients with metastatic PTC harboring the BRAF(V600E) mutation. Vemurafenib was initially dosed at 240-360 mg twice a day, later escalated to 720 mg twice a day. Response evaluation was performed every 8 weeks per Response Evaluation Criteria in Solid Tumors (RECIST).Among the three patients, one had a confirmed partial response with reduction of pulmonary target lesions by 31%, and the duration of response was 7.6 months before the disease progressed in the lungs and the bones. The time to progression was 11.7 months. The other two patients had stable disease, and the time to progression was 13.2 and 11.4 months, respectively.Vemurafenib appears to have a promising clinical activity in patients with metastatic PTC, and our data suggest that the BRAF(V600E) mutant kinase is a relevant target for therapy in this patient population. Further investigation of inhibitors of mutated BRAF kinase in patients with PTC in a phase II study 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
BRAF act mut thyroid gland cancer sensitive Vemurafenib Phase I Actionable In a Phase I trial, Zelboraf (vemurafenib) demonstrated safety and efficacy in metastatic papillary thyroid cancer patients carrying BRAF activating mutations (PMID: 23489023). 23489023
BRAF act mut thyroid gland papillary carcinoma sensitive Vemurafenib Phase I Actionable In a Phase I trial, Zelboraf (vemurafenib) demonstrated safety and efficacy in metastatic papillary thyroid cancer patients carrying BRAF activating mutations (PMID: 23489023). 23489023