Value Evaluation Of Pembrolizumab As A Single Agent In The First-line Treatment Of Advanced Non-small Cell Lung Cancer

Background:Non-small cell lung cancer(NSCLC)is the most common type of lung cancer,and its morbidity and mortality rate both rank first among malignant tumors in China.Pembrolizumab(Pembro)has been shown to be effective in the first-line treatment of advanced NSCLC,but there is currently a lack of relevant value evaluation.Purpose:This study comprehensively evaluates the effecacy,safety and cost-utility of Pembro in the first-line treatment of NSCLC,and aims to establish a scientific and complete drug value evaluation system to promote clinical rational use of drugs and return drugs to clinical value;and provide pharmacoeconomic evidence,and scientific and reasonable suggestions for market access and medical insurance access of highvalue innovative drugs in the future.Method:1.Use STATA14.0 software to conduct meta-analysis on the efficacy and safety evidence of Pembro,and conduct a summary analysis for the evidence that cannot be used for meta-analysis;2.Based on the RCT of the Chinese population(KEYNOTE-42 Chinese study),use Tree Age Pro 2019 software to establish a partitioned survival model(PSM),and evaluate the use of Pembro single-drug versus traditional platinum-based chemotherapy for the first-line Cost-effectiveness of treatment of NSCLC.Results:1.Efficacy(1)Compared with traditional platinum-based chemotherapy,Pembro can benefit patients with longer OS,and the higher the PD-L1 expression level of the patient,the more significant the efficacy of Pembro;(2)For the two endpoints of progression-free survival(PFS)and objective response rate(ORR),Pembro can only be used in programmed death receptor ligand 1(programmed death receptor ligand 1,PD-L1)≥50% of the subgroups showed significant differences.2.Safety(1)In terms of the incidence of treatment-related adverse events(trAEs)of any grade and trAEs of grade 3-5,Pembro is safer than traditional platinum-based chemotherapy;trAEs of any grade are mainly including fatigue,pyrexia,pruritus,rash,and hypothyroidism;trAEs of grade 3-5 mainly include rash,alanine aminotransferase increased,and anemia;(2)In terms of the incidence of immune-mediated adverse events(imAEs)of any grade,the safety of Pembro is inferior to traditional platinum-based chemotherapy;imAEs of any grade mainly include hypothyroidism,pneumonitis,hyperthyroidism and severe skin reactions.3.Cost-utility(1)Base case results: From the perspective of the Chinese healthcare system,regardless of the patient’s PD-L1 expression level,when the willingness-to-pay(WTP)threshold is (?)217,341/quality-adjusted life year(quality-Adjusted life year,QALY),compared with traditional platinum chemotherapy,treatment with Pembro is not costutility;(2)Scenario analysis results: Even in the case of charity donation(for patients with family financial difficulties)using Pembro,compared with chemotherapy,it is still not cost-utility,only when the unit price of Pembro drops to 20% and used in the population with PD-L1≥50%,the program has a certain economic efficiency;(3)Sensitivity analysis results: The results of one-way deterministic sensitivity analysis(Deterministic Sensitivity Analysis,DSA)show that the drug costs of Pembro,the drug costs of pemetrexed,and the utility values have significant influence on the incremental cost-effectiveness ratio(incremental cost–utility ratio,ICUR);the results of probabilistic sensitivity analysis(PSA)show that the probability of Pembro being cost-utility compared with chemotherapy is 0%.Conclusion:In terms of efficacy,compared with traditional platinum-based chemotherapy,Pembro can benefit patients with longer OS,but for the PFS and ORR,Pembro only showed significant differences in the subgroup of people with PD-L1≥50%.In terms of safety,the incidence of any grade of trAEs and 3-5 trAEs caused by Pembro monotherapy was lower,but the incidence of any grade of imAEs caused by Pembro was higher.In terms of cost-utility,compared with platinum-based chemotherapy treatments,regardless of the patient’s PD-L1 expression level,the use of Pembro for treatment was not cost-utility.When the unit price of Pembro was reduced by 80%,Pembro could be cost-utility when used in the population with PD-L1≥50%.