FGFR4 alterations predict efficacy of immune checkpoint inhibitors in non-small cell lung cancer

Immune checkpoint inhibitors (ICIs) are the new standard of care for advanced non-small cell lung cancer (aNSCLC). However, ICIs are not effective in many patients, and biomarkers are needed to guid treatment. A discovery study at Shanghai Pulmonary Hospital found that ICI-treated patients carrying FGFR4 mutations had better ORR (50.0% versus 19.4%; p=0.057) and improved median progression-free survival (13.17 versus 3.17 months; HR 0.37; p=0.04) when compared to FGFR4 wild-type patients. In publicly available validation cohorts, FGFR4 alterations correlated with higher ORR (100% versus 31%; p=0.028), longer median PFS (NR versus 6.07 months; HR 0.05; p=0.039), and longer median overall survival (NR versus11 months; HR 0.28; p=0.02). FGFR4 alterations correlated with higher TMB levels and more CD8+ T cells in tumor stroma. The authors conclude that FGFR4 alterations may serve as potential independent predictors of ICI efficacy in NSCLC.