For patients with advanced or metastatic NSCLC harboring specific oncogenic driver mutations such as ALK, ROS1, NTRK, and RET fusions, as well as mutations in HER-2, BRAF, KRAS, EGFR, and MET exon 14, frontline targeted therapies can be considered irrespective of PD-L1 levels (Fig. 6).263 Certainly, aiming to alleviate symptoms with early palliative treatments,264 such as nutritional support, radiotherapy, surgery, cryotherapy, microwave, or radiofrequency ablation, can enhance the quality of life in patients with metastatic NSCLC. This evidence concerns the gene CD274 and non-small cell lung carcinoma.