Sorafenib was effective in patients with non-small cell lung cancer and a KRAS mutation, but survival rates were reportedly unsatisfactory.

Patients with lung cancer and a KRAS mutation are believed to have a poor prognosis and may not benefit from treatment with epidermal growth factor receptor tyrosine kinase inhibitors.

"There is a great need for targeted treatment options for patients with non-small cell lung cancer (NSCLC) with a KRAS mutation," says study author Wouter W. Mellema, MD, a doctoral candidate at VU University Medical Center in Amsterdam.

In the Phase 2, multicenter study conducted in the Netherlands, researchers assigned 57 patients with NSCLC and a KRAS mutation to 400 mg of sorafenib twice daily.

At six weeks, Mellema and colleagues reported a rate of no progression of 52.6%. Fifteen patients stopped treatment before six weeks—10 of whom stopped due to clinical progression. Median progression-free survival was 2.3 months, and median overall survival was 5.3 months. The researchers reported that 14 patients are still alive.

"Sorafenib could be a useful drug in this patient population by inhibiting the growth-stimulating signal of the RAS protein," Mellema says. "However, although sorafenib showed relevant activity, the outcome was unsatisfactory."

Mellema and his team had conducted a pilot study in 10 patients, which showed promising results. The results of the Phase 2 study were less optimistic.

Mellema suggested that the KRAS mutation causes early progression by stimulating cell growth through an alternative pathway.

Release Date: Jan. 9, 2012
Source: VU University Medical Center