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Optimizing combination dabrafenib and trametinib therapy in BRAF mutation‐positive advanced melanoma patients: Guidelines from Australian melanoma medical oncologists
Author(s) -
Atkinson Victoria,
Long Georgina V.,
Menzies Alexander M.,
McArthur Grant,
Carlino Matteo S.,
Millward Michael,
RobertsThomson Rachel,
Brady Benjamin,
Kefford Richard,
Haydon Andrew,
Cebon Jonathan
Publication year - 2016
Publication title -
asia‐pacific journal of clinical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 29
eISSN - 1743-7563
pISSN - 1743-7555
DOI - 10.1111/ajco.12656
Subject(s) - dabrafenib , trametinib , medicine , melanoma , mek inhibitor , oncology , tolerability , radiation therapy , combination therapy , adverse effect , drug , vemurafenib , cancer research , pharmacology , kinase , metastatic melanoma , mapk/erk pathway , biology , microbiology and biotechnology
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.