Does mutation status predict the effectiveness of targeted therapies in NSCLC?

This study examined the use of a type of targeted therapy called immune checkpoint inhibitors to treat advanced non-small-cell lung cancer (NSCLC). The authors concluded that for patients who had a genetic mutation (change) called KRAS, ICIs were more effective than chemotherapy. They suggest that the presence of KRAS mutations could predict the type of treatment a patient gets.

Treatment of non-small-cell lung cancer (NSCLC) is now focused more on targeted therapy where treatment is specific for the individual patient. One new type of treatment are immune checkpoint inhibitors (ICIs). ICIs act by blocking a protein present on tumor cells which then activates the immune system to fight the tumor.

Methods of predicting which treatments may be effective would be beneficial. One possible marker is the presence of a KRAS mutation (change), which is common in NSCLC. Studies thus far show conflicting results on whether this would be a good marker or not.

This meta-analysis aimed to determine whether the presence of a KRAS mutation affects the outcome of ICIs in patients with advanced NSCLC. Three trials were included with a combined 509 patients. Of these, 138 patients had KRAS mutations and 371 did not.

For patients who had KRAS mutations, ICIs resulted in 36% improved overall survival (OS, time from beginning trial until death) compared to chemotherapy. For patients who did not have KRAS mutations, ICIs did not improve OS compared to chemotherapy.

The authors concluded that for patients with KRAS mutation positive NSCLC, ICIs are an effective treatment. They suggested that the presence of KRAS mutations could be a biomarker to determine whether to use ICIs or not.