Combined RET and MEK Inhibition as a Treatment for Fusion-Positive NSCLC With Acquired Fusion: A Case Report.

fusions are present in 1% to 2% of NSCLCs. Although RET inhibitors like selpercatinib are effective, resistance inevitably develops. We present the case of a 28-year-old female with recurrent NSCLC and a fusion treated with selpercatinib. Testing at the time of progression revealed a new :BRAF fusion. She was then treated with a combination of selpercatinib and trametinib, which led to a likely partial response, despite the combination demonstrating side effects. This case report details the first known instance of NSCLC with a fusion developing resistance by means of a fusion, treated with combined RET and MEK inhibition.