Cost-utility Analysis Of PD-1/PD-L1 Inhibitors As First-line Treatment For Advanced Lung Cancer

ObjectiveTo evaluate the cost-utility of pembrolizumab,atezolizumab and durvalumab as first-line therapy for advanced lung cancer,and provide references for clinicians to choose appropriate therapeutic drugs and policy makers to allocate health resources rationally.MethodsCombined with clinical trial data,disease treatment methods and costs,Tree Age Pro software was used to simulate the disease treatment process and resource assumption of advanced non-small cell lung cancer(NSCLC)and extensive-stage small cell lung cancer(ES-SCLC).The incremental cost-utility ratio(ICUR)was the main indication and three times per capital gross domestic product was set as the willingness-to-pay(WTP)threshold to evaluate the cost-utility of intervention measures.A regimen could be regarded as cost-effective so long as the ICUR less than the WTP threshold:(1)Based on the different programmed death ligand 1(PD-L1)levels respond differently to pembrolizumab treatment,we extracted survival data from Kaplan-Meier curves with different PD-L1 levels,and constructed three Markov models to assess the cost-utility of pembrolizumab for advanced NSCLC patients with PD-L1≥50%,≥20% and ≥1%,respectively.(2)The treatment-related costs of the US and China were collected,respectively,to evaluate and compare the cost-utility of atezolizumab plus chemotherapy as first-line treatment for advanced NSCLC in different countries.The drug price was gained from the Red Book and appraised from the US payer perspective.The listing price of atezolizumab was undetermined in China,we estimated its price according to the price ratio of pembrolizumab in the US and China;we acquired the bidding price of other drugs from yaozhi.com to conduct cost-utility analysis from China healthcare system perspective and provide a reference for the listing of atezolizumab in China.(3)To improve the accuracy of model fitting,the pseudo-individual patient data were generated from Kaplan-Meier curve.The maxim likelihood method was applied to fit the survival curve,five survival function were used to parameterize the model and the optimal fitting function was selected to construct model to evaluate the cost-utility of durvalumab combined with chemotherapy for ES-SCLC.Results1.Compared with chemotherapy,patients treated with pembrolizumab provided an additional 1.13,1.01,and 0.59 quality-adjust life years(QALYs)in patients with PD-L1 expression levels of ≥50%,≥20% and ≥1%,with corresponding incremental cost of $53,784,$47,479,and $39,827,respectively.The resultant ICURs were$47,596,$47,184,and $68,061/QALY,in three expression levels of PD-L1,respectively,all of which did not exceed the WTP threshold of 180,000/QALY.Probabilistic sensitivity analysis outcome supported that pembrolizumab exhibited evident advantage over chemotherapy in cost-utility.One-way sensitivity analysis found that ICURs were most sensitive to the utility value.2.For advanced NSCLC patients,treated with atezolizumab/carboplatin/nabpaclitaxel(ACnP)is associated with an expected 0.99 QALYs as compared to 0.67 QALYs for carboplatin/nab-paclitaxel(Cn P)therapy.In the US,the incremental costs was $105,617 and ICUR was $333,199/QALY,which exceeded the WTP threshold of$180,000/QALY in the US.In China,the incremental costs was $50,494 and ICUR was $159,299/QALY,which also higher than the WTP threshold of $29,383/QALY in China.Parameters that greatly impacted the ICUR were the price of atezolizumab and utility values.The Cn P exhibited 98.6% and 100% probability of being as a cost-effective treatment option compared with ACnP in the US and China,respectively.However,reducing atezolizumab’s aquicision cost by 43.4% in the US could make ACnP more cost-effective compared to Cn P.In China,ACnP was cost-effective only when the price of atezolizumab lower than 807.5/1200 mg.3.Compared with etoposide/platinum(EP),durvalumab plus EP(DEP)treated ES-SCLC was projected to increase life expectancy by 0.86 LYs(1.73 vs.0.87)and0.44 QALYs(0.93 vs.0.49).The incremental cost was $91,127 and the corresponding ICUR was $206,139/QALY.The result was most sensitive to variation of durvalumab acquisition cost.Probabilistic sensitivity analysis revealed that the probability of DEP to be a cost-effective regimen was 29.5% at a WTP threshold of $180,000/QALY in the US.In the case of reducing the price of durvalumab by 13.6%,DEP was more cost-effective than EP.Conclusion1.For treatment-naive,advanced NSCLC patients with PD-L1≥50%,≥20% and≥1%,pembrolizumab was estimated to be cost-effective compared with chemotherapy in the context of the US payer.2.Adding atezolizumab to Cn P is not cost-effective for advanced NSCLC at base-case scenario in the US.Same conclusion was draw from the China healthcare system perspective.The price of atezolizumab lower than 807.5/1200 mg could enhance cost-utility of ACnP in China.Our study can provide a reference for the listing of atezolizumab in China.3.From the perspective of the US payer,adding durvalumab to chemotherapy is estimated to be not cost-effective compared with chemotherapy alone for untreated ES-SCLC patients.