OBJECTIVES:To evaluate the cost-effectiveness of osimertinib as first-line and second-line therapy for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC) in China. METHODS:Markov model was developed to simulate the first-line and second-line therapy of EGFR mutation-positive advanced NSCLC, including three health states: progression-free survival, progression disease and death. Two treatment strategies were compared in this model: osimertinib first-line followed by pemetrexed+cisplatin and gefitinib first-line followed by osimertinib second-line. The model cycle was 20years. Clinical data and utility values were derived from published literatures. Data of costs were obtained from Sichuan Cancer Hospital & Institute, Chengdu, PR China. All costs and outcomes were discounted at 5% per annum. Quality-adjusted life year(QALY) was used to indicate health benefits. The cost-effectiveness ratio(CER) and incremental cost-effectiveness ratio(ICER) were performed with TreeAge Pro 2019. One way sensitivity analysis and probabilistic sensitivity analysis were conducted to assess model stability. RESULTS:The life expectancy of patients receiving osimertinib first-line followed by pemetrexed+cisplatin was 39.1 months, which was 34.7 months in patients receiving gefitinib first-line followed by osimertinib second-line in our model simulation. The CER of osimertinib as first-line therapy strategy and as second-line therapy strategy were $27072.5/QALY and $34856.65/QALY respectively. The estmated ICER in the base case scenario was $-33727.97/QALY gained with osimertinib first-line followed by pemetrexed+cisplatin. The probabilistic sensitivity analysis showed that the probability of osimertinib first-line followed by pemetrexed+cisplatin being cost-effectiveness was 94.9% at the willingness-to-pay threshold of $29307. One way sensitivity analysis indicated that the utility of survival after osimertinib first-line therapy progression was the principal consideration affecting robustness of outcomes. CONCLUSIONS:Osimertinib first-line followed by pemetrexed+cisplatin could gain better cost-effectiveness than gefitinib first-line followed by osimertinib second-line. Osimertinib should be a good choice as first-line therapy for EGFR mutation-positive advanced NSCLC in China.