Testing biological therapy in treating KRAS-mutant NSCLC

This study aimed to assess the efficacy and safety of anti-cancer drug trametinib (Mekinist) in comparison to docetaxel (Taxotere) in treating patients with KRAS-mutation-positive advanced non-small-cell lung cancer (NSCLC). The study concluded that there was no difference in efficacy between trametinib and docetaxel however trametinib had a higher incidence of side effects.

Mutations (changes) in a gene called the KRAS gene can lead to cancer, including NSCLC. There are currently no targeted therapies to combat this type of cancer. Trametinib is a drug used to block proteins called MEK’s, which are involved in cancer. This drug has been shown previously to be effective in KRAS-mutation-positive NSCLC. It is not clear whether it is more effective than the chemotherapy docetaxel (Taxotere). 

134 patients with KRAS-mutation-positive stage 4 (spread to other areas of the body) NSCLC were included in the study. Patients had to have progressed despite at least 1 prior chemotherapy treatment for advanced NSCLC. The study aimed to assess the progression free survival (PFS, length of time from beginning treatment until disease progression), safety, objective response rate (ORR, patients with tumors that decrease by at least 50%) and duration of response.

Patients were randomly assigned into two groups. 89 patients in group 1 were treated with trametinib. 45 patients in group 2 were treated with docetaxel.

There was no difference in PFS or ORR between the groups. Group 1 had average response duration of 7 weeks while group 2 had average response duration of 12 weeks. 12% of patients in group 1 saw a partial response to treatment (such as tumor shrinkage) compared to 5% of group 2.

All patients in both groups had at least 1 side effect. The most common side effects in group 1 included rash, diarrhea, high blood pressure, nausea, fatigue, shortness of breath and pneumonia. Group 1 had a higher incidence of shortness of breath and pneumonia than group 2. There were no fatalities due to side effects in group 2 however 4 patients died from side effects in group 1.

The study concluded that trametinib and docetaxel had similar rates of effectiveness. However, trametinib had a higher rate of side effects.

This study assessed the drugs as single agent therapies. This does not rule out the possibility that trametinib is effective in combination with another cancer therapy.

This study was funded by GlaxoSmithKline, the manufacturers of trametinib.