AffiliationThe Christie NHS Foundation Trust, Manchester, UK
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AbstractThe RAS-RAF-MEK-ERK pathway regulates processes involved in the proliferation and survival of cells. KRAS mutations, prevalent in approximately 30% of patients with non-small-cell lung cancer (NSCLC), result in constitutive activation of the pathway. Selumetinib (AZD6244, ARRY-142886) is a potent and selective inhibitor of MEK1/2 which has demonstrated significant efficacy in combination with docetaxel in patients with KRAS mutant pretreated advanced NSCLC. Several trials in combination with other chemotherapy and targeted therapy regimens in lung cancer are ongoing. We review the development of selumetinib in patients with NSCLC, summarize the pharmacodynamic, pharmacokinetic and tolerability characteristics, and the available clinical trial data to understand the role of selumetinib in the treatment of NSCLC.
CitationSelumetinib in the treatment of non-small-cell lung cancer. 2016: Future Oncol
- Study Design and Rationale for a Randomized, Placebo-Controlled, Double-Blind Study to Assess the Efficacy and Safety of Selumetinib in Combination With Docetaxel as Second-Line Treatment in Patients With KRAS-Mutant Advanced Non-Small Cell Lung Cancer (SELECT-1).
- Authors: Jänne PA, Mann H, Ghiorghiu D
- Issue date: 2016 Mar
- A randomized phase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small-cell lung cancer (NSCLC)†.
- Authors: Blumenschein GR Jr, Smit EF, Planchard D, Kim DW, Cadranel J, De Pas T, Dunphy F, Udud K, Ahn MJ, Hanna NH, Kim JH, Mazieres J, Kim SW, Baas P, Rappold E, Redhu S, Puski A, Wu FS, Jänne PA
- Issue date: 2015 May
- BYL719, a selective inhibitor of phosphoinositide 3-Kinase α, enhances the effect of selumetinib (AZD6244, ARRY-142886) in KRAS-mutant non-small cell lung cancer.
- Authors: Ku BM, Jho EH, Bae YH, Sun JM, Ahn JS, Park K, Ahn MJ
- Issue date: 2015 Feb
- A phase I study of selumetinib (AZD6244/ARRY-142866), a MEK1/2 inhibitor, in combination with cetuximab in refractory solid tumors and KRAS mutant colorectal cancer.
- Authors: Deming DA, Cavalcante LL, Lubner SJ, Mulkerin DL, LoConte NK, Eickhoff JC, Kolesar JM, Fioravanti S, Greten TF, Compton K, Doyle AG, Wilding G, Duffy A, Liu G
- Issue date: 2016 Apr
- Selumetinib with and without erlotinib in KRAS mutant and KRAS wild-type advanced nonsmall-cell lung cancer.
- Authors: Carter CA, Rajan A, Keen C, Szabo E, Khozin S, Thomas A, Brzezniak C, Guha U, Doyle LA, Steinberg SM, Xi L, Raffeld M, Tomita Y, Lee MJ, Lee S, Trepel JB, Reckamp KL, Koehler S, Gitlitz B, Salgia R, Gandara D, Vokes E, Giaccone G
- Issue date: 2016 Apr