Selumetinib plus docetaxel shows KRAS-mutant NSCLC potential

Dec 3 2012

By Lynda Williams, Senior medwireNews Reporter

The addition of selumetinib to docetaxel therapy may boost the survival of patients with KRAS-mutant non-small-cell lung cancer (NSCLC), suggest study findings published in The Lancet Oncology.

The median overall survival of patients with stage IIIB-IV disease given selumetinib plus docetaxel (n=44) was significantly higher than that of patients given docetaxel plus placebo (n=43), at 9.4 versus 5.2 months, giving a hazard ratio (HR) for mortality of 0.80, report Pasi Jänne (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and co-authors.

Selumetinib plus docetaxel was also associated with significantly better median progression-free survival than docetaxel plus placebo, at 5.3 versus 2.1 months, and a HR for progression of 0.58.

Furthermore, an objective total or partial response to treatment was achieved by 37% of selumetinib plus docetaxel patients compared with none of the controls, a significant difference.

However, the researchers note that selumetinib was also associated with a significantly greater rate of grade 3 or higher adverse events, affecting 82% of treated patients compared with 67% of patients given docetaxel and placebo.

The most common grade 3-4 reactions in the selumetinib and placebo groups were neutropenia (67 vs 55%), febrile neutropenia (18 vs 0%), dyspnea (0 vs 12%), and asthenia (9 vs 0%).

"Our findings suggest that the addition of selumetinib to docetaxel provides clinical benefit for patients with KRAS-mutant advanced NSCLC," Jänne et al summarize

"However, this is a phase 2 study and requires further validation in a large phase 3 clinical trial to elucidate the effect on overall survival and to provide further guidance on management of the toxicity of the combination."

They explain that KRAS, the most common mutation in NSCLC, has as yet no specifically targeted therapies, but that selumetinib acts on downstream proteins in the RAS-RAF-MEK-ERK signaling pathway. This is the first study to test the MEK1/MEK2 inhibitor in this particular population.

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