title: Dabrafenib in the treatment of metastatic or unresectable melanoma.
abstract: Dabrafenib is a potent inhibitor of mutant BRAF. Trials to date have shown it to be well tolerated, with significant activity in unresectable stage III or IV metastatic melanoma. Overall response rates of approximately 50% were seen in addition to improved progression-free and overall survival of 6 and 18 months, respectively. Preclinical studies suggested that combining BRAF and MEK inhibition would increase response rates and decrease toxicity. Clinical trials with the combination of dabrafenib and trametinib have improved progression-free and overall survival in interim analyses. Future improvements in responses and outcomes will depend on additional combination strategies, possibly employing immunotherapy.
authors.affiliation: Princess Margaret Cancer Centre, University Avenue, Toronto, M5G 2M9, Ontario, Canada.
authors.forename: Leila
authors.initials: L
authors.lastname: Khoja
authors.forename: David
authors.initials: D
authors.lastname: Hogg
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D018572:Disease-Free Survival; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010091:Oximes / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D010091:Oximes; D047428:Protein Kinase Inhibitors; C561627:dabrafenib
keywords: BRAF; dabrafenib; efficacy; metastatic melanoma; toxicity; trametinib