New Testing Methods Improve Detection and Treatment Selection Lung Cancer Mutations

Researchers have developed better ways to find a specific genetic change in lung cancer that affects how patients should be treated. This genetic change, called MET exon 14 skipping, occurs in 1-4% of non-small cell lung cancer patients but is often missed by standard testing methods.

The study examined 1,143 lung cancer patients and found 46 cases with MET exon 14 mutations. These genetic changes are tricky to detect because they come in many different forms. Four cases would have been missed using only standard DNA testing, but were caught using additional testing methods that look at both DNA and RNA.

Finding these mutations is important because it changes how doctors treat patients. People with MET exon 14 mutations often don’t respond well to immunotherapy, even when other tests suggest they should. Instead, they may benefit more from targeted drugs like capmatinib and crizotinib that specifically block the MET protein.

In this study, 15 patients received MET-targeted drugs. About 44% saw their tumors shrink, and patients lived an average of 5.5 months without their cancer getting worse. Thirteen patients received immunotherapy instead, with only 30% responding and cancer staying stable for an average of 4 months.

Interestingly, 67% of patients with MET mutations had high levels of a protein called PD-L1, which usually predicts good response to immunotherapy. However, these patients still didn’t respond well to immunotherapy, showing that the MET mutation overrides other factors.

The researchers found that smokers with MET mutations responded better to immunotherapy than non-smokers. Many patients also had additional genetic changes, with 42% having other mutations alongside their MET alteration.

This research emphasizes that comprehensive genetic testing using multiple methods is essential to ensure lung cancer patients receive the most effective treatment for their specific tumor type.