Hanna NH, Schneider BJ, Temin S, et al. - In this work, evidence-based recommendations updating the 2017 ASCO guideline on systemic therapy for patients suffering from stage IV non–small-cell lung cancer (NSCLC) without driver alterations were provided. For cases with stage IV NSCLC with driver alterations, a guideline update will be issued separately. Patients without driver alterations in epidermal growth factor receptor or anaplastic lymphoma kinase are eligible for the application of these recommendations. Single-agent pembrolizumab has been advised by the Expert Panel for patients having high programmed death ligand 1 (PD-L1) expression (tumor proportion score [TPS] ≥ 50%) and non–squamous cell carcinoma (non-SCC). Pembrolizumab/carboplatin/pemetrexed was recommended for most patients having non-SCC and either negative (0%) or low positive (1% to 49%) PD-L1. Single-agent pembrolizumab was advised for patients with high PD-L1 expression (TPS ≥ 50%) and SCC. Pembrolizumab/carboplatin/(paclitaxel or nab-paclitaxel) or chemotherapy was recommended by the Expert Panel for most cases with SCC and either negative (0%) or low positive PD-L1 (TPS 1% to 49%). These recommendations are conditional based on histology, PD-L1 status, and/or the presence or absence of contraindications.