Dabrafenib and trametinib for the treatment of non-small cell lung cancer

ABSTRACT

Introduction: BRAF^V600E mutations occur in 1–2% of lung adenocarcinomas and act as oncogenic drivers via the mitogen-activated protein kinase (MAPK) pathway. These mutations are mutually exclusive from the more common, epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements and have been associated with poor outcomes and a lower response to platinum-based chemotherapy.

Areas covered: Dabrafenib is a potent adenosine-triphosphate-competitive inhibitor of BRAF kinase and is selective for the BRAF^V600E mutation in kinase panel screening, cell lines, and xenografts. The efficacy and safety of dabrafenib alone or in combination with the MEK inhibitor trametinib has been demonstrated in a number of clinical trials and herein, we discuss this data and outline the current and future role of BRAF/MEK inhibition in the management of advanced lung cancer.

Expert commentary: Responses rates with combination of dabrafenib/trametinib are approximately 63–64% and interestingly occur in both smokers and non-smokers but toxicities require dose reductions in the real world for the majority of patients.

KEYWORDS:

• BRAF mutations
• Dabrafenib
• Trametinib
• Non-Small cell lung cancer

Declaration of interest

RJ Kelly has served on an advisory board and a data monitoring committee for Novartis. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.