OBJECTIVES:   This study aimed to evaluate the cost-effectiveness of pembrolizumab compared with docetaxel in patients in patients with previously treated advanced NSCLC with PD-L1 positive tumors (TPS>=50%). The analysis was conducted from a US third-party payer perspective. METHODS:   <span">A partitioned-survival model was developed using data from patients from the KEYNOTE-010 (KN010) clinical trial. The model used KM estimates of PFS and OS from the trial for patients treated with pembrolizumab 2mg/kg and docetaxel 75kg/m2 with extrapolation based on fitted parametric functions and long-term registry data. Quality-adjusted life years (QALYs) were derived based on EQ-5D data from KN010 using a time to death approach.Costs of drug acquisition/administration, adverse event management, and clinical management of advanced NSCLC were included in the model. The base-case analysis used a time horizon of 20 years. Costs and health outcomes were discounted at a rate of 3% per year. A series of one-way and probabilistic sensitivity analyses was performed to test the robustness of the result. RESULTS:   Base case results project for PD-L1 positive (TPS>=50%) patients treated with pembrolizumab a mean survival of 2.25 years. For docetaxel, a mean survival time of 1.07 years was estimated. Expected QALYs were 1.71 and 0.76 for pembrolizumab and docetaxel, respectively. The incremental cost per QALY gained with pembrolizumab vs. docetaxel is $168,619/QALY, which is cost-effective in the US using a threshold of three times GDP per capita. CONCLUSIONS:   Pembrolizumab improves the QALYs and is a cost-effective option compared to docetaxel in PD-L1 positive (TPS>=50%) pre-treated advanced NSCLC patients in the US.