Pharmacoeconomics Analysis Of Two Schemes Of Targeted Therapy In Maintenance Treatment In NSCLC Based On Decision Model

OBJECTIVELung cancer,with a high mortality rate,is one of the most challenging diseases in effective therapy.Small cell lung cancer and non-small cell lung cancer(NS CLC),accounting for 80%,is the highest morbidity subtype of lung cancer.At present,the pharmacotherapy of NSCLC includes chemical medicines and targeted drug therapy.It is shown that targeted drugs have the characteristics of low toxicity compared with chemotherapy drugs.Clinically,targeted drugs mainly includes the epidermal growth factor receptor(EGFR)inhibitors and vascular endothelial growth factor(VEGF)monoclonal antibody.Erlotinib,also known as Tarceva,is a kind of EGFR kinase inhibitors,which is mainly used for patients with EGFR mutations,and has an unique curative effect.The American food and drug administration and European drug administration recommend that this drug could be two and three-line main drugs in NSCLC.Compared with the first-line chemotherapy,tarceva can obviously prolong progression-free survive(PFS)and overall survive(OS)of patients with NSCLC.Bevacizumab,is a kind of VEGF monoclonal antibody,whose main function is to be the inhibition of vascular endothelial growth factor,thereby blocking the spread of the tumor.Clinical trials demonstrated that bevacizumab application helps extend the patient’s PFS and OS,is of great significance combining with paclitaxel and carboplatin.Bevacizumab and erlotinib are different drugs in mechanism.Mutation or overexpression of EGFR was a significant factor of proliferation,metastasis,neovascularization.There existed some relations between EGFR pathway and VEGF pathway,The neovascularization partly was caused by EGRF.Besides,some EGFR inhibitor could down-regulated expression of VEGF.And it could reduce the drug-tolerance problems caused by a single targeted drug,which ulteriorly reduces the drug-waste phenomenon.Combination of them should be more effective than single in theory.Some clinical trials and evidence-based medicine suggest that combination of different target drugs could prolong PFS and OS comparing with single.At present,the pharmacoeconomics researches mainly focus on comparing targeted drugs with chemotherapy drugs or comparing different targeted drugs,and lacking the research on comparing combination of different mechanisms of targeting drug with single one.Despite the combined application of two molecular targeted drugs brings excellent clinical curative effects,the high price of molecular targeted drugs makes it difficult to extensively use in clinical practice.This pressure was remitted in a certain degree by the charity activities sponsored by Roche pharmaceuticals company,but,as a result of eligibility,not so many people were in benefits.Thus,there are two main aims of this research:one is to evaluate whether the combination arm could be accessed into clinical application which could be accepted by most of Chinese patients;and the other is to evaluate whether the combination arm could be accessed into medicine care system.METHODSThis research based on the hybrid study model,which means it obtains clinical data from "A service of the U.S.National Institutes of Health" and retrospectively analyzed bevacizumab co-work with EGFR and bevacizumab alone to receive the more economic and effective treatment regimen.Cost-utility analysis method is a suitable method for chronic diseases such as non-small cell lung cancer.Thus,the final output result is cost-utility.Meanwhile,we showed a systemic evaluation of the two arms.Because of the requirements of forecasting the cost-utility,we must adopt mathematical model,such as Markov model,to derive the potential consequence..This study adopted SAS programming software to obtain the transition probability of research and analyzed the results in nonlinear iterative method,in order to verify the rationality of the Markov model under the research,and verify whether the weibull function fits to this study.We also employed rock analysis to gain the consequence.And we employed one-way sensitivity analysis and monte-carlo simulation analysis to test the stability of the results.In addition,we come to the conclusion that which arm was the optimal regimen and fit to Chinese WTP.RESULTSWe employed markov model for 120 stages to obtain the stage cost,stage effectiveness,cumulative cost and cumulative effectiveness.The results showed that the QALYs of Bev.+Erl.arm and Bev.alone arm were 1.049 and 0.887 respectively;the cumulative cost of two arms were ￥ 1,227,865.33 yuan and ￥761,024.27 yuan respectively.The result also showed that the ICUR was 2,881,734.94 yuan/QALY,which was much higher than 3-time mean GDP,which meaned it did not have Cost-utility.CONCLUSIONPharmacoeconomics analysis of two schemes of targeted therapy in maintenance treatment in NSCLC is based on Markov model.This study shows that:the Union arm doesn’t worth spreading in China.