title: Optimizing combination dabrafenib and trametinib therapy in BRAF mutation-positive advanced melanoma patients: Guidelines from Australian melanoma medical oncologists.
abstract: BRAF mutations occur commonly in metastatic melanomas and inhibition of mutant BRAF and the downstream kinase MEK results in rapid tumor regression and prolonged survival in patients. Combined therapy with BRAF and MEK inhibition improves response rate, progression free survival and overall survival compared with single agent BRAF inhibition, and reduces the skin toxicity that is seen with BRAF inhibitor monotherapy. However, this combination is associated with an increase in other toxicities, particularly drug-related pyrexia, which affects approximately 50% of patients treated with dabrafenib and trametinib (CombiDT). We provide guidance on managing adverse events likely to arise during treatment with combination BRAF and MEK inhibition with CombiDT: pyrexia, skin conditions, fatigue; and discuss management of CombiDT during surgery and radiotherapy. By improving tolerability and in particular preventing unnecessary treatment cessations or reduction in drug exposure, best outcomes can be achieved for patients undergoing CombiDT therapy.
authors.affiliation: Princess Alexandra Hospital, Greenslopes Private Hospital and University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Victoria
authors.initials: V
authors.lastname: Atkinson
authors.affiliation: Melanoma Institute Australia, Royal North Shore and Mater Hospitals, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Georgina V
authors.initials: GV
authors.lastname: Long
authors.affiliation: Melanoma Institute Australia, Royal North Shore and Mater Hospitals, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Menzies
authors.affiliation: Peter MacCallum Cancer Centre and Cabrini Health, Melbourne, Victoria, Australia.
authors.forename: Grant
authors.initials: G
authors.lastname: McArthur
authors.affiliation: Westmead Hospital, Sydney, New South Wales, Australia.
authors.forename: Matteo S
authors.initials: MS
authors.lastname: Carlino
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia and Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Millward
authors.affiliation: Queen Elizabeth Hospital, Adelaide, South Australia, Australia.
authors.forename: Rachel
authors.initials: R
authors.lastname: Roberts-Thomson
authors.affiliation: Peter MacCallum Cancer Centre and Cabrini Health, Melbourne, Victoria, Australia.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Brady
authors.affiliation: Westmead Hospital and Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Kefford
authors.affiliation: The Alfred Hospital, Melbourne, Victoria, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Haydon
authors.affiliation: Olivia Newton John Cancer Wellness & Research Centre, Austin Health Melbourne, Victoria, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cebon
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001315:Australia; D003875:Drug Eruptions / Q000209:etiology / Q000628:therapy; D005076:Exanthema / Q000139:chemically induced / Q000628:therapy*; D005334:Fever / Q000139:chemically induced / Q000628:therapy*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors; D008495:Medical Oncology / Q000379:methods; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics*; D009154:Mutation; D010091:Oximes / Q000008:administration & dosage / Q000009:adverse effects; D017410:Practice Guidelines as Topic; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics*; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects; D011744:Pyrimidinones / Q000008:administration & dosage / Q000009:adverse effects; D012878:Skin Neoplasms; D000096142:Cutaneous Malignant Melanoma
chemical_list: D007093:Imidazoles; D010091:Oximes; D011728:Pyridones; D011744:Pyrimidinones; C560077:trametinib; D048493:Proto-Oncogene Proteins B-raf; D020930:MAP Kinase Kinase Kinases; C561627:dabrafenib
keywords: BRAF; MEK; dabrafenib; melanoma; pyrexia; trametinib