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|Ref Type||Journal Article|
|Authors||Mangana J, Levesque MP, Karpova MB, Dummer R|
|Title||Sorafenib in melanoma.|
|Journal||Expert opinion on investigational drugs|
|Abstract Text||Sorafenib is an orally available multi-kinase inhibitor that inhibits tumor proliferation by targeting multiple kinases including the vascular endothelial growth factor receptors VEGFR1, VEGFR2, VEGFR3 and the platelet-derived growth factor receptor PDGFR, and it targets tumor progression by inhibiting FLT3, C-Kit and BRAF. Since BRAF mutations are frequent in melanoma, sorafenib was investigated in various Phase I, II and III clinical trials. The drug is well tolerated with mild to moderate adverse effects, which are mostly limited to cutaneous toxicity, diarrhea and fatigue.Systematic literature review of the randomized trials using PubMed was performed. Original articles were reviewed and citations from those were also considered. Additionally, clinical trial databases were examined to identify and summarize ongoing trials of sorafenib in melanoma patients.Sorafenib as a monotherapy or in combination with chemotherapy is of limited use. Combining it with dacarbazine doubled the response rate and the progression-free survival in metastatic melanoma patients. Unfortunately, these results have never been evaluated in large randomized Phase III clinical trials. According to the trials conducted so far a subpopulation of patients experience substantial benefit, therefore it is essential to identify biomarkers to select the subgroups of patients that are more likely to respond to sorafenib. Furthermore, other less frequent subtypes such as mucosal or ocular melanoma still constitute promising targets; academic institutions are currently launching investigator-initiated trials in these indications.|
|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||melanoma||no benefit||Sorafenib||Phase II||Actionable||In a Phase II study, Nexavar (sorafenib) displayed negligible efficacy in melanoma patients with BRAF mutations (PMID: 16880785, PMID: 22394203).||22394203 16880785|
|BRAF V600E||melanoma||no benefit||Sorafenib||Phase II||Actionable||In a Phase II study, Nexavar (sorafenib) displayed negligible efficacy in melanoma patients with BRAF V600E mutations (PMID: 16880785, PMID: 22394203).||22394203 16880785|