Missing content? – Request curation!
Request curation for specific Genes, variants, or PubMed publications.
Have questions, comments or suggestions? - Let us know!
Email us at : firstname.lastname@example.org
|Ref Type||Journal Article|
|Authors||Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, O'Dwyer PJ, Lee RJ, Grippo JF, Nolop K, Chapman PB|
|Title||Inhibition of mutated, activated BRAF in metastatic melanoma.|
|Journal||The New England journal of medicine|
|Date||2010 Aug 26|
|Abstract Text||The identification of somatic mutations in the gene encoding the serine-threonine protein kinase B-RAF (BRAF) in the majority of melanomas offers an opportunity to test oncogene-targeted therapy for this disease.We conducted a multicenter, phase 1, dose-escalation trial of PLX4032 (also known as RG7204), an orally available inhibitor of mutated BRAF, followed by an extension phase involving the maximum dose that could be administered without adverse effects (the recommended phase 2 dose). Patients received PLX4032 twice daily until they had disease progression. Pharmacokinetic analysis and tumor-response assessments were conducted in all patients. In selected patients, tumor biopsy was performed before and during treatment to validate BRAF inhibition.A total of 55 patients (49 of whom had melanoma) were enrolled in the dose-escalation phase, and 32 additional patients with metastatic melanoma who had BRAF with the V600E mutation were enrolled in the extension phase. The recommended phase 2 dose was 960 mg twice daily, with increases in the dose limited by grade 2 or 3 rash, fatigue, and arthralgia. In the dose-escalation cohort, among the 16 patients with melanoma whose tumors carried the V600E BRAF mutation and who were receiving 240 mg or more of PLX4032 twice daily, 10 had a partial response and 1 had a complete response. Among the 32 patients in the extension cohort, 24 had a partial response and 2 had a complete response. The estimated median progression-free survival among all patients was more than 7 months.Treatment of metastatic melanoma with PLX4032 in patients with tumors that carry the V600E BRAF mutation resulted in complete or partial tumor regression in the majority of patients. (Funded by Plexxikon and Roche Pharmaceuticals.)|
|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 V600E||thyroid gland papillary carcinoma||sensitive||Vemurafenib||Case Reports/Case Series||Actionable||In a Phase I trial, Zelboraf (vemurafenib) treatment resulted in a complete or partial response in three papillary thyroid carcinoma patients harboring BRAF V600E, with one patient having a response that lasted for 8 months who remained progression-free for 12 months, and another two patients having a stable disease that lasted for 11 and 13 months, respectively (PMID: 20818844; NCT00215605).||20818844|
|BRAF V600E||melanoma||sensitive||Vemurafenib||Phase I||Actionable||In a Phase I trial, Zelboraf (vemurafenib) treatment resulted in an overall response rate of 81% (26/32; 2 complete responses, 24 partial responses), and inhibition of tumor Erk and Ccnd1, and reduced cell proliferation in metastatic melanoma patients harboring BRAF V600E (PMID: 20818844; NCT00215605).||20818844|