As for adenocarcinomas, large cell carcinomas and not otherwise specified NSCLC the same biomarkers should be evaluated; however, first-line therapy differs from squamous NSCLC when PD-L1 positive and EGFR- ALK and ROS-1 negative or of unknown status (Nivolumab, Pembrolizumab, Atezolizumab or systemic therapy with Docetaxel, Gemcitabine or Ramucirumab + Docetaxel). This evidence concerns the gene CD274 and large cell carcinoma.