In this study, we evaluated the activation of CDK4/6-Cyclin D-Rb pathway in NSCLC cell lines resistant to osimertinib, with acquired resistance to first-line (PC9BRAFG469A cell line) or second-line therapy (PC9T790MclA, PC9T790MclC and PC9T790MC797S cell lines) and intrinsically resistant (HCC827EMT and HCC827GR5 cell lines). This evidence concerns the gene RB1 and non-small cell lung carcinoma.