The results from a randomized Phase 2 placebo-controlled study comparing the efficacy of Selumetinib in combination with Docetaxel with Docetaxel alone in the second-line treatment of 87 patients prospectively selected with KRAS-mutant, locally advanced or metastatic non-small cell lung cancer, have been presented.
This is the first completed randomized combination trial with a MEK inhibitor.
The study's primary endpoint of overall survival has demonstrated a numerically greater increase in survival in favor of Selumetinib in combination with Docetaxel versus Docetaxel alone, but did not reach statistical significance.
The key secondary endpoints of progression-free survival, objective response rate, and alive and progression-free at 6 months were all demonstrated with statistical significance, showing improvement in favor of Selumetinib in combination with Docetaxel versus Docetaxel alone.
Non-small cell lung cancer ( NSCLC ) is one of the leading causes of cancer-related mortality in the United States. In 2011, the estimated new cases of NSCLC in the U.S. are 186,000. Most patients are diagnosed with advanced, stage IIIb or IV disease and are not amenable to surgery.
The overall two-year survival rate for patients with advanced NSCLC is 10-20%.
In patients with NSCLC, major components of cell signaling pathways, such as the Ras-Raf-MEK-MAPK pathway, and components of the normal cell cycle are frequently altered. Approximately 20% of current NSCLC patients have tumors with KRAS mutations, which represents a sub-population of nearly 60,000 NSCLC patients in the U.S. with poor prognosis and a high unmet medical need.
Selumetinib is an anti-cancer drug in Phase 2 development in a range of tumors. It is a small molecule MEK inhibitor that targets a key position in the Ras-Raf-MEK-ERK signaling pathway. MEK has been shown to be frequently activated in cancer, in particular in tumors that have mutations in the RAS and RAF pathways.
Source: Array BioPharma, 2011
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