Cost-effectiveness analysis of tyrosine kinase inhibitors(erlotinib,gefitinib,afatinib and osimertinib)as first-line therapy for epidermal growth factor receptor-mutated advanced non-small cell lung cancer

Gefitinib,erlotinib,afatinib and osimertinib have been recommended as the first-line treatment for epidermal growth factor receptor(EGFR)-mutated advanced non-small cell lung cancer(NSCLC),whereas no studies have compared the cost-effectiveness of these four tyrosine kinase inhibitors(TKIs)simultaneously in China.In the present study,we aimed to estimate the cost-effectiveness of erlotinib,gefitinib,afatinib and osimertinib for untreated EGFR-mutated advanced NSCLC.A Markov model was constructed to compare the 10-year impact of four TKIs for patients with treatment-naive EGFR-mutated advanced NSCLC from the perspective of the Chinese medical system.Clinical data and utility values were derived from published literature,and costs were obtained from Chinese official websites.The primary output indicator was the incremental cost-effectiveness ratio(ICER).Sensitivity analyses were performed to test the robustness of the model.We found that afatinib was estimated to spend the lowest cost with minimum life-years(LYs),while osimertinib was the most expensive regimen with maximum LYs.The ICER of gefitinib versus afatinib was$732/quality-adjusted life-year(QALY),which was less than the willingness-to-pay(WTP)of$29382/QALY.Compared with gefitinib,erlotinib yielded a higher cost and a shorter lifetime,hence it was identified as a dominated strategy.Then,osimertinib was compared to gefitinib,which produced an ICER of$71330/QALY,exceeding the WTP.It suggested that gefitinib was the most cost-effective regimen as the first-line treatment for EGFR-mutated advanced NSCLC.Decreasing the osimertinib price or increasing the WTP threshold to$68558/QALY might enhance the favorability of the outcome,by which osimertinib might become more cost-effective.One-way sensitivity analysis manifested that the model was robust.

Influence of CYP2C9*3 and CYP4F2 rs2108622 gene polymorphisms on over-anticoagulation and bleeding complications of warfarin therapy in Chinese patients:a cohort study

In this retrospective cohort study,we aimed to identify the influence of the CYP2C9*3 and CYP4F2 rs2108622 gene alleles on over-anticoagulation and bleeding complications associated with warfarin therapy.A total of 196 patients were included,including 80 males,the mean age was 50.8±10.7 years,and the average follow-up was 26.9±11.8 months.These patients underwent heart valve replacement surgery in the Cardiovascular Surgery of Fujian Provincial Hospital between January 2018 and August 2019,who took warfarin for at least 3 months and had target international normalized ratio(INR)between 1.8 and 2.5.Genotypes of CYP2C9*3 and CYP4F2 rs2108622 genes were tested by polymerase chain reaction(PCR)-gene sequencing technique.SPSS19.0 software was utilized to analyze the association between genotypes and warfarin-related over-anticoagulation and bleeding complications.Of the 434 patient-years,18 severe bleedings and 59 mild ones occurred in 31 patients.Patients with CYP2C9*1/*3 were associated with a higher over-anticoagulation risk compared with the*1/*1 carriers(hazard rate(HR)7.10;95%confidence interval(CI):2.54–19.79,P<0.001).The CYP4F2 rs2108622 mutant genotype did not cause significant increase in bleeding risk(HR 0.89;95%CI:0.43–1.82,P=0.74)or over-anticoagulation(HR 0.43;95%CI:0.16–1.13,P=0.09).Meanwhile,Kaplan-Meier survival curves showed that the time to over-anticoagulation in CYP2C9*1/*3 carriers was significantly shorter compared with the*1/*1 carriers(log-rank test,P<0.001),while that in CYP4F2 rs2108622 mutant genotype patients was longer compared with the wild-type patients(P=0.05).CYP2C9*3 and CYP4F2 rs2108622 might be major predictive factors of over-anticoagulation for warfarin therapy in Chinese patients.