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Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib

by Rutkowski, Piotr , Crist, Wendy , Krajsova, Ivana , Lichinitser, Michael , Nathan, Paul , Ribas, Antoni , Drucis, Kamil , Karaszewska, Boguslawa , Legos, Jeff , Hauschild, Axel , Rubin, Stephen D , Schadendorf, Dirk , Chiarion-Sileni, Vanna , Schachter, Jacob , Mackiewicz, Andrzej , Robert, Caroline , Long, Georgina V , Grange, Florent , Sun, Peng , Mortier, Laurent , Wolter, Pascal , Flaherty, Keith , Dummer, Reinhard , Stroiakovski, Daniil , Martin, Anne-Marie , Little, Shonda M , Lorigan, Paul

in Adolescent / Adult / Aged / Aged, 80 and over / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Antitumor activity / Cancer therapies / Clinical outcomes / Female / Humans / Imidazoles - administration & dosage / Imidazoles - adverse effects / Indoles - adverse effects / Indoles - therapeutic use / Inhibitor drugs / Intention to Treat Analysis / Kaplan-Meier Estimate / Kinases / Male / Medical treatment / MEK inhibitors / Melanoma / Melanoma - drug therapy / Melanoma - mortality / Melanoma - secondary / Metastases / Metastasis / Middle Aged / Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors / Mutation / Oximes - administration & dosage / Oximes - adverse effects / Protein Kinase Inhibitors - administration & dosage / Protein Kinase Inhibitors - adverse effects / Proto-Oncogene Proteins B-raf - antagonists & inhibitors / Proto-Oncogene Proteins B-raf - genetics / Pyridones - administration & dosage / Pyridones - adverse effects / Pyrimidinones - administration & dosage / Pyrimidinones - adverse effects / Skin Neoplasms - drug therapy / Skin Neoplasms - pathology / Squamous cell carcinoma / Sulfonamides - adverse effects / Sulfonamides - therapeutic use / Survival Analysis / Targeted cancer therapy / Toxicity / Young Adult

2015

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Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib

2015

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Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib

2015

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Journal Article

Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib

Rutkowski, Piotr,

Crist, Wendy,

Krajsova, Ivana,

Lichinitser, Michael,

Nathan, Paul,

Ribas, Antoni,

Drucis, Kamil,

Karaszewska, Boguslawa,

Legos, Jeff,

Hauschild, Axel,

Rubin, Stephen D,

Schadendorf, Dirk,

Chiarion-Sileni, Vanna,

Schachter, Jacob,

Mackiewicz, Andrzej,

Robert, Caroline,

Long, Georgina V,

Grange, Florent,

Sun, Peng,

Mortier, Laurent,

Wolter, Pascal,

Flaherty, Keith,

Dummer, Reinhard,

Stroiakovski, Daniil,

Martin, Anne-Marie,

Little, Shonda M,

Lorigan, Paul

2015

Overview

In patients with melanomas containing activating BRAF mutations, the combination of a BRAF inhibitor and a MEK inhibitor improved overall survival, as compared with a BRAF inhibitor alone, and was associated with many fewer second skin tumors. The treatment of metastatic melanoma is rapidly evolving. The potent and specific BRAF inhibitors vemurafenib and dabrafenib, as compared with chemotherapy, have significantly improved response rates, along with progression-free and overall survival, in patients with metastatic melanoma with BRAF V600E or V600K mutations. 1 , 2 However, acquired resistance to BRAF inhibitors frequently develops through reactivation of the mitogen-activated protein kinase (MAPK) pathway, resulting in a median progression-free survival of 6 to 8 months. 2 – 5 In addition, the use of BRAF inhibitors may result in the development of secondary skin tumors, originating from a paradoxical activation of the MAPK pathway in cells . . .

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Publisher

Massachusetts Medical Society

Subject

Adolescent

/ Adult

/ Aged

/ Aged, 80 and over

/ Antineoplastic Combined Chemotherapy Protocols - adverse effects

/ Antineoplastic Combined Chemotherapy Protocols - therapeutic use

/ Antitumor activity