摘要:The clinical trial of Keynote-604 showed that pembrolizumab plus chemotherapy could generate clinical benefits for extensive-stage small-cell lung cancer (ES-SCLC). We aim to assess the efficacy and cost of pembrolizumab combined with chemotherapy in the first-line treatment setting of ES-SCLC from the United States (US) payers’ perspective. Methods A synthetical Markov model was used to evaluate cost and effectiveness of pembrolizumab plus platinum-etoposide(EP) versus EP in first-line therapy for ES-SCLC from the data of Keynote-604. Lifetime costs life-years(LYs), quality adjusted LYs(QALYs) and incremental cost-effectiveness ratios(ICERs) were estimated. One-way and probabilistic sensitivity analyses were performed. Furthermore, we performed subgroup analysis. Results Pembrolizumab plus EP resulted in additional 0.18 QALYs(0.32 LYs) and corresponding incremental costs $113,625, resulting an ICER of $647,509 per QALY versus EP. The price of pembrolizumab had a significant impact on ICER. Probabilistic sensitivity analysis indicated that pembrolizumab combined chemotherapy may become a cost-effective option with a probability of 0%. Besides, subgroup analysis suggested that all subgroups were not cost-effective. Conclusion From the perspective of the US payer, pembrolizumab plus EP is not a cost-effective option for first-line treatment patients with ES-SCLC at a WTP threshold of $150,000 per QALY. Supplementary Information The online version contains supplementary material available at 10.1186/s12962-021-00329-w.