Details

Autor(en) / Beteiligte

• Long, Georgina V
• Stroyakovskiy, Daniil
• Gogas, Helen
• Levchenko, Evgeny
• de Braud, Filippo
• Larkin, James
• Garbe, Claus
• Jouary, Thomas
• Hauschild, Axel
• Grob, Jean Jacques
• Chiarion Sileni, Vanna
• Lebbe, Celeste
• Mandalà, Mario
• Millward, Michael
• Arance, Ana
• Bondarenko, Igor
• Haanen, John B.A.G
• Hansson, Johan
• Utikal, Jochen
• Ferraresi, Virginia
• Kovalenko, Nadezhda
• Mohr, Peter
• Probachai, Volodymyr
• Schadendorf, Dirk
• Nathan, Paul
• Robert, Caroline
• Ribas, Antoni
• DeMarini, Douglas J
• Irani, Jhangir G
• Casey, Michelle
• Ouellet, Daniele
• Martin, Anne-Marie
• Le, Ngocdiep
• Patel, Kiran
• Flaherty, Keith

Titel

Combined BRAF and MEK Inhibition versus BRAF Inhibition Alone in Melanoma

Ist Teil von

• The New England journal of medicine, 2014-11, Vol.371 (20), p.1877-1888

Ort / Verlag

United States: Massachusetts Medical Society

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• The addition of a MEK inhibitor to a BRAF inhibitor improved response rates by nearly 16 percentage points (from 51% to 67%) and improved progression-free survival by 0.5 months (from 8.8 to 9.3 months). Targeted inhibition of the RAF–MEK–ERK (MAPK) pathway with BRAF inhibitors dabrafenib or vemurafenib, as compared with chemotherapy, improves the progression-free and overall survival of patients who have metastatic melanoma with BRAF V600 mutations. 1 , 2 However, resistance develops in a majority of patients, resulting in a median progression-free survival of 6 to 7 months. 3 , 4 Most reported resistance mechanisms reactivate the MAPK pathway. 5 – 7 In addition, BRAF-inhibitor–induced paradoxical activation of the MAPK pathway 8 – 10 can result in secondary cancers, including cutaneous squamous-cell carcinoma, and may reactivate RAS-mutant tumors. 11 – 13 Independently, single-agent trametinib, a MEK inhibitor, improves the overall survival of patients . . .