Immune checkpoint inhibitors for RET fusion non-small cell lung cancer: hopes and challenges

Immune ch eckpoint inhibitors (ICIs) represent a milestone in advanced nonsmall cell lung cancer (NSCLC). Nevertheless, NSCLC with known oncogenic drivers has been overlooked in most studies evaluating anti-programmed death-1/programmed death ligand 1. Rearranged during transfection proto-oncogene (RET) gene fusion was identified in 1-2% of NSCLC patients. More recently, two selective RET inhibitors, selpercatinib and pralsetinib, demonstrated higher efficacy and good tolerability. In contrast, the activity of ICIs in RET fusion NSCLC has not been well characterized. Here, we analyzed the clinical data of ICIs and discussed the suitable time to introduce ICIs in RET fusion NSCLC. Finally, we put forward future strategies to adequately maximize the efficacy of ICIs treatment in patients with RET fusion NSCLC in the upcoming era of combination immunotherapies.