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Phase III Program Evaluates Selumetinib in Lung Cancer
MEK inhibitor is co-administered with docetaxel (October 22)
The first patient has been enrolled in a phase III clinical trial program for selumetinib (AstraZeneca), an oral selective MEK (mitogen-activated protein/extracellular signal-regulated kinase kinase) inhibitor that is being investigated as second-line therapy in patients with advanced or metastatic non–small-cell lung cancer (NSCLC) whose tumors are KRAS mutation-positive.
The SELumetinib Evaluation as Combination Therapy-1 (SELECT-1) trial is a randomized, double-blind, placebo-controlled study that will evaluate the safety and efficacy of selumetinib plus docetaxel as a second-line therapy in locally advanced or metastatic KRAS mutation-positive NSCLC — a genetic subtype of lung cancer associated with a poor prognosis and limited treatment options. The study is designed to evaluate progression-free survival (PFS) and overall survival.
The decision to advance selumetinib to phase III studies in NSCLC followed the results from a randomized phase II trial that evaluated the combination of selumetinib with standard-of-care docetaxel compared with docetaxel alone in patients with KRAS mutation-positive NSCLC. The study demonstrated a high and durable response rate of 37.2% with selumetinib and docetaxel versus 0% with docetaxel alone (P < 0.0001), which translated into a statistically significant improvement in PFS of 5.3 versus 2.1 months, respectively (hazard ratio, 0.58; P < 0.014).
MEK is part of the mitogen-activated protein kinase (MAPK) pathway, which is frequently activated in cancer and is elevated in many different solid tumor types, including those featuring the KRAS mutation, which is present in 20% of human cancers and in 20% to 30% of NSCLC tumors.
Source: AstraZeneca; October 22, 2013.