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Review
. 2018 Jan-Dec:12:1753466618767611.
doi: 10.1177/1753466618767611.

Dabrafenib in combination with trametinib in the treatment of patients with BRAF V600-positive advanced or metastatic non-small cell lung cancer: clinical evidence and experience

Arjun Khunger  1 , Monica Khunger  2 , Vamsidhar Velcheti  3
Affiliations
Review

Dabrafenib in combination with trametinib in the treatment of patients with BRAF V600-positive advanced or metastatic non-small cell lung cancer: clinical evidence and experience

Arjun Khunger et al. Ther Adv Respir Dis. 2018 Jan-Dec.

Abstract

Mutations in the BRAF oncogene are found in 2-4% of all non-small cell lung cancer (NSCLC) patients. The most common activating mutation present within the BRAF oncogene is associated with valine substitution for glutamate at position 600 (V600E) within the BRAF kinase. BRAF-targeted therapies are effective in patients with melanoma and NSCLC harboring BRAF V600E mutation. In both melanoma and NSCLC, dual inhibition of both BRAF and the downstream mitogen-activated protein kinase (MEK) improves response rates compared with BRAF inhibition alone. BRAF-MEK combination therapy (dabrafenib plus trametinib) demonstrated tolerability and efficacy in a recent phase II clinical trial and was approved by the European Medicines Agency and United States Food and Drug Administration for patients with stage IV NSCLC harboring BRAF V600E mutation. Here, in this review, we outline the preclinical and clinical data for BRAF and MEK inhibitor combination treatment for NSCLC patients with BRAF V600E mutation.

Keywords: BRAF V600E; dabrafenib; non-small cell lung cancer (NSCLC); trametinib.

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Conflict of interest statement

Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: V Velcheti: Consultant/Advisory Role: BMS, Genentech, Astrazenca, Foundation Medicine/Novartis/Takeda Oncology.

Rest of the authors: have no disclosures.

Figures

Figure 1.
Figure 1.
Mechanism of action of dabrafenib and trametinib: binding of BRAF and MEK inhibitors generates a blockade point in MAPK pathway at two different levels, inhibiting oncogenic downstream signaling and causing cell cycle arrest. MAPK: mitogen-activated protein kinase.
See this image and copyright information in PMC

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