Cost-utility Analysis Of Atezolizumab Plus Bevacizumab Versus Sorafenib As First-line Therapy In Unresectable Or Metastatic Hepatocellular Carcinoma

Objective:Atezolizumab plus bevacizumab substantially extends life expectancy for unresectable or metastatic hepatocellular carcinoma patients.Its cost-utility(CU)was previously evaluated based on primary trial analyses.The present analysis describes CU incorporating the latest follow-up data from the perspectives of Chinese healthcare system and U.S.payers.Method:(1)Base-case analyses:A Markov model and a partitioned survival(PS)model with 1 month cycle in 10 years horizon were adopted based on a phase III clinical trial(IMbrave 150).Costs and utility values were derived from literature and databases.The transition probabilities and proportions were estimated by calculation.Total costs,total life years,total quality adjusted life years(QALY),incremental cost-utility ratios(ICUR),incremental net health benefits and incremental net monetary benefits were main outputs of the models.The economics of two strategies were judged by comparing the ICUR value with the willingness-to-pay threshold(WTPT).(2)Sensitivity analyses:① One-way sensitivity analyses:Each parameter was changed individually over prespecified ranges.②Two-way sensitivity analyses:To assess the interplay between the top two parameters with the greatest influence on ICUR,two-way sensitivity analyses were performed by varying two parameter values simultaneously.③Subgroup analyses:Subgroup analyses were conducted by varying subgroup-special hazard ratios for overall survival and progression-free survival reported in the IMbrave 150 trial.④Probabilistic sensitivity analyses:1000 iterations of second-order Monte Carlo simulations were carried out with each key parameter varied simultaneously with fixed statistical distributions.(3)Price exploration analyses:Exploring appropriate prices for atezolizumab plus bevacizumab.Results:(1)Base-case analyses:From the Chinese healthcare system perspective,the base-case estimates of ICURs for atezolizumab plus bevacizumab versus sorafenib in the Markov model and PS model were $267366/QALY and $262725/QALY,respectively.From the US payer perspective,the base-case estimates of ICURs for atezolizumab plus bevacizumab versus sorafenib in the Markov model and PS model were $491347/QALY and $486409/QALY,respectively.All ICURs exceeded the WTPT($31499/QALY in China and $150000/QALY in the US).(2)Sensitivity analyses:All sensitivity analyses confirmed that the base-case results were stable.(3)Price exploration analyses:From the Chinese healthcare system perspective,if the prices of atezolizumab plus bevacizumab were reduced by 81.47%or 81.56%(Markov model or PS model)to 88.73%or 88.96%(Markov model or PS model),the ICURs were the same as the WTPT of $31499/QALY to $10499.7/QALY.From the US payer perspective,if the prices of atezolizumab plus bevacizumab were reduced by 48.21%or 48.51%(Markov model or PS model)to 55.26%or 55.72%(Markov model or PS model),the ICURs were the same as the WTPT of $150000/QALY to$100000/QALY.Conclusion:From the perspectives of Chinese healthcare system and U.S.payers,atezolizumab plus bevacizumab is determined not to be as cost-effective as sorafenib in the first-line setting for unresectable or metastatic hepatocellular carcinoma patients at the adopted thresholds of $31499/QALY,$150000$/QALY.