Background Pembrolizumab significantly improves progression-free survival (PFS) (median 10.3 months) and overall survival (OS) (median 30.0 months) in selected patients with previously untreated advanced non–small-cell lung cancer (NSCLC) with a PD-L1 tumor proportion score (TPS) ≥ 50% and without EGFR/ALK aberrations. Data in real life conditions are missing. Methods This was a cross-sectional, retrospective study of untreated advanced NSCLC patients with TPS ≥ 50% and without EGFR/ALK aberrations, from 9 French hospitals in Brittany area. The study included 115 patients and analysis focused on 108 patients. At index, the main characteristics of our cohort were: median age [range] 66.7 [37 to 87] years, 71 % male, 23.1 % performans status (P.S) 2, 88.8 % current or former smokers. 87.1 % had Stage IV at diagnosis and 9.2 % had untreated brain metastasis. 23.4% had mutations (KRAS, MET, BRAF and ROS 1). We used Kaplan-Meier analysis for PFS and described tolerability. Results With a median follow-up of 7.1 months, median PFS was 10.1 months (95% confidence interval [CI], 8.8 to 11.4), (range, and 0.6 to 18.5 months). The objective response rate was 58,2% (complete response: 2.7 % and partial response: 55.5 %). Disease control rate was 72.1%. The estimated rate of OS at 6 months was 86.6 %. Treatment-related adverse events of grade 3 (AE) occurred in 7.4% of patients. There was no grade 4 or 5 AE and mean time between first administration of pembrolizumab and clinico-biological AE was 13.9 (± 9.7) weeks. Our data are immature to appreciate OS. Conclusions In a real life cohort of patients (PS 2, untreated brain metastasis), with advanced NSCLC and PD-L1 expression on at least 50% of tumor cells, pembrolizumab demonstrates similar PFS with KEYNOTE-024 phase III trial. Legal entity responsible for the study Renaud Descourt. Funding Association Bretonne de Cancerologie Thoracique (ABCT). Disclosure R. Corre: Travel / Accommodation / Expenses, Officer / Board of Directors: bms. G. Robinet: Advisory / Consultancy: MSD; Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): BMS; Research grant / Funding (institution): Roche. R. Descourt: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: takeda; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy: Novartis; Advisory / Consultancy: BMS; Travel / Accommodation / Expenses: Pfizer. All other authors have declared no conflicts of interest. Linguistic correction