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Combined Vemurafenib and Cobimetinib in BRAF-Mutated Melanoma
Ist Teil von
The New England journal of medicine, 2014-11, Vol.371 (20), p.1867-1876
Ort / Verlag
United States: Massachusetts Medical Society
Erscheinungsjahr
2014
Quelle
MEDLINE
Beschreibungen/Notizen
The combination of inhibitors to BRAF and MEK improved response rates and progression-free survival among patients with metastatic melanoma. Some toxicity was increased, but the incidence of second skin cancers was drastically reduced by the combination therapy.
Approximately 50% of metastatic cutaneous melanomas harbor a
BRAF
V600 mutation, resulting in constitutive activation of the mitogen-activated protein kinase (MAPK) pathway.
1
,
2
These discoveries led to the development of agents that specifically target this driver mutation. The BRAF inhibitor vemurafenib (Zelboraf, Genentech) was approved worldwide on the basis of results from a phase 3 trial showing improved progression-free survival and overall survival, as compared with chemotherapy alone; the relative reduction in the risk of death was 63% and in the risk of disease progression was 74%.
3
Similar results were also reported for another BRAF inhibitor, dabrafenib,
4
which has also . . .