Second, small molecule TKIs targeting a growing number of gain-of-function molecular targets, such as EGFR, BRAF V600E, MET exon 14 skipping mutations, and ALK-, ROS1-, and neurotrophic receptor tyrosine kinase (NTRK)- or RET-gene fusions have been shown to improve PFS and OS with favorable toxicity profiles compared to platinum-containing combination chemotherapy as first-line systemic therapy in ~ 25% of NSCLC patients (Table 8). This evidence concerns the gene RET and non-small cell lung carcinoma.