Comprehensive Clinical Evaluation Of EGFR Inhibitors In The Treatment Of Advanced Non-small Cell Lung Cancer

Objective: Lung cancer is the most common cancer of all cancer types and the leading cause of cancer death.The first part of the study was patient-centered and evaluated the safety,innovation,suitability and accessibility of EGFR inhibitors in the treatment of patients with advanced NON-small cell lung cancer,providing reference for the formulation of health policies and clinical decision-making and promoting clinical rational drug use.Methods: From the safety dimension,the domestic and foreign specifications of drugs that can inhibit EGFR mutation were searched through Milnet,Pharmacointelligence and the official website of the US Food and Drug Administration,and multiple literature databases such as Pub Med,Embase,Science Direct,CNKI and Wanfang Data Knowledge Service platform were searched by computer.Clinical trials,reviews,post-market evaluation,adverse reaction monitoring and other literature related to drug safety were obtained,and the safety of EGFR inhibitors was evaluated by the risk of administration route,pre-market safety,post-market safety,and the use of special populations.In the accessibility dimension study,a tertiary comprehensive public hospital in Anhui Province was selected to collect the sales and sales volume of EGFR inhibitors for consecutive 5 years from January 2016 to December 2020 by retrospective data analysis.The data were obtained from the electronic medical record system of the hospital.The collected drug costs and annual sales volume were recorded and calculated by Microsoft Excel 2010,and THE DDDs,DDDc and B /A of EGFR inhibitors were calculated for analysis and comparison.In the appropriateness dimension,the real world prescription rationality analysis method was used to evaluate the clinical use of drugs in patients,and the rationality of drug use in patients’ prescriptions was analyzed.In this study,100 prescriptions for NON-small cell lung cancer（NSCLC）were collected annually from sample hospitals through HIS system during 2016-2020,with a total of500 prescriptions.Prescription comments were carried out according to the contents stipulated in Prescription Management Measures and referring to drug instructions.Problems existing in the process of prescription issuance by physicians were retrospectively analyzed,and inappropriate prescription of drug use was analyzed.The innovation dimension study analyzed the technological innovation and industrial innovation of EGFR-TK inhibitors by searching relevant literature and data.Results: In terms of drug accessibility,the study found that the EGFR inhibitors used in NSCLC samples mainly included gefitinib,erlotinib,ectinib hydrochloride,oxitinib,afatinib and androtinib hydrochloride.The top three drugs in the list of DDDs were gefitinib,ectinib and erlotinib.From 2016 to 2020,gefitinib B/A was equal to 1 only in2017,and B/A was greater than 1.0 in the other four years.The B/A of erlotinib from2016 to 2017 was less than 1.0,and the B/A of erlotinib from 2018 to 2020 was more than 1.0 for three consecutive years.The B/A of oxitinib was around 1.0 for three consecutive years from 2018 to 2020,indicating good synchronization of drug selection.The results of drug use suitability analysis showed that there were 25 cases of irrational drug use in 500 prescriptions,accounting for 5%.Conclusions: EGFR inhibitors are currently highly selective drugs for the treatment of non-small cell lung cancer,and the specific conditions of patients,the effectiveness and safety of drugs should be taken into account in the selection of drugs,and the factors of drug accessibility and suitability should be taken into account in the use.Objective: With the changes of modern drug policy,health insurance negotiation and budget impact analysis,rational drug selection in the treatment of patients with advanced NSCLC needs to take into account the clinical efficacy and the economic burden of the disease.The drug utilization study in the first part of this project showed that gefitinib was the most frequently used EGFR inhibitor from 2016 to 2020,and its drug synchronization analysis also showed that its drug cost decreased year by year or its patient acceptance was good.In this part,cost-effectiveness analysis was conducted on gefitinib monotherapy and combined chemotherapy for non-small cell lung cancer.Based on the comprehensive clinical evaluation of EGFR inhibitor drugs,the basis for rational clinical drug use was provided to promote the wide application of pharmacoeconomic methods in clinical decision-making.Methods: Markov model was established to evaluate the health and economic effects of first-line chemotherapy gefitinib and combined chemotherapy in the treatment of advanced non-small cell lung cancer.Clinical data,cost and utility data are obtained from published literature or from the real world;Quality-adjusted life years and incremental cost-benefit ratio were used as the analysis results.Sensitivity analysis was used to verify the robustness of the model.Results: The average cost of gefitinib and combination chemotherapy was 62882.83 USD and 84,509.30 USD,respectively.The QALY values of the two groups were 1.70 and 1.93,respectively.The ICERs for combined chemotherapy and gefitinib alone were$95135.50.Univariate sensitivity analysis showed that the utility value of progressive status had the greatest influence on the outcome,followed by the cost of supporting treatment and the utility value of progression-free survival.Probabilistic sensitivity analysis showed that if the willingness to pay threshold in China was $33,300 /QALY,the combination chemotherapy regimen was less likely to be preferred than gefitinib monotherapy.Conclusions: This study suggests that from the perspective of the Chinese health system,combination chemotherapy is not a cost-effective comprehensive evaluation option for patients with advanced NSCLC with EGFR mutations.The findings could help clinicians make the best treatment decisions for patients with advanced NSCLC.