Atezolizumab plus bevacizumab versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma: a cost-effectiveness analysis.
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ABSTRACT:
SUBMITTER: Hou Y
PROVIDER: S-EPMC7743015 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
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Atezolizumab plus bevacizumab versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma: a cost-effectiveness analysis.
Cancer communications (London, England) 20201107 12
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Project description:ImportanceTreatment with atezolizumab plus bevacizumab may prolong overall survival among patients with unresectable hepatocellular carcinoma. However, to our knowledge, the cost-effectiveness of using this high-priced therapy for this indication is currently unknown.ObjectiveTo evaluate the cost-effectiveness of atezolizumab plus bevacizumab to treat unresectable hepatocellular carcinoma from the US payer perspective.Design, setting, and participantsThis economic evaluation used a partitioned survival model consisting of 3 discrete health states to assess the cost-effectiveness of treatment of hepatocellular carcinoma with atezolizumab plus bevacizumab vs sorafenib. The characteristics of patients in the model were similar to patients in a phase 3, open-label randomized clinical trial (IMbrave150) who had unresectable hepatocellular carcinoma and had not previously received systemic treatment. Key clinical data were generated from the IMbrave150 trial conducted between March 15, 2018, and January 30, 2019, and cost and health preference data were collected from the literature.Main outcomes and measuresCosts, quality-adjusted life-years (QALYs), incremental cost-utility ratios, incremental net health benefits, and incremental net monetary benefits were calculated for the 2 treatment strategies. Subgroup, 1-way sensitivity, and probabilistic sensitivity analyses were performed.ResultsTreatment of hepatocellular carcinoma with atezolizumab plus bevacizumab added 0.530 QALYs and resulted in an incremental cost of $89 807 compared with sorafenib therapy, which had an incremental cost-utility ratio of $169 223 per QALY gained. The incremental net health benefit was -0.068 QALYs, and the incremental net monetary benefit was -$10 202 at a willingness-to-pay threshold of $150 000/QALY. The probabilistic sensitivity analysis indicated that treatment with atezolizumab plus bevacizumab achieved a 35% probability of cost-effectiveness at a threshold of $150 000/QALY. One-way sensitivity analysis revealed that the results were most sensitive to the hazard ratio of overall survival. The subgroup analysis found that treatment with atezolizumab plus bevacizumab was associated with preferred incremental net health benefits in several subgroups, including patients with hepatitis B and C.Conclusions and relevanceAtezolizumab plus bevacizumab treatment is unlikely to be a cost-effective option compared with sorafenib for patients with unresectable hepatocellular carcinoma. Reducing the prices of atezolizumab and bevacizumab may improve cost-effectiveness. The economic outcomes also may be improved by tailoring treatments based on individual patient factors.
| S-EPMC7905498 | biostudies-literature
Project description:The IMbrave 150 trial revealed that atezolizumab plus bevacizumab (atezo-bev) improves survival in patients with unresectable hepatocellular carcinoma (HCC) (1 year survival rate: 67.2% vs. 54.6%). We assessed the cost-effectiveness of atezo-bev vs. sorafenib as first-line therapy in patients with unresectable HCC from the US payer perspective. Using data from the IMbrave 150, we developed a Markov model to compare the lifetime cost and efficacy of atezo-bev as first-line systemic therapy in HCC with those of sorafenib. The main outcomes were life-years, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). Atezo-bev demonstrated a gain of 0.44 QALYs, with an additional cost of USD 79,074. The ICER of atezo-bev was USD 179,729 per QALY when compared with sorafenib. The model was most sensitive to the overall survival hazard ratio and body weight. If we assumed that all patients at the end of the IMbrave 150 trial were cured of HCC, atezo-bev was cost-effective (ICER USD 53,854 per QALY). However, if all patients followed the Surveillance, Epidemiology, and End Results data, the ICER of atezo-bev was USD 385,857 per QALY. Reducing the price of atezo-bev by 20% and 29% would satisfy the USD 150,000/QALY and 100,000/QALY willingness-to-pay threshold. Moreover, capping the duration of therapy to ≤12 months or reducing the dosage of bev to ≤10 mg/kg would render atezo-bev cost-effective. The long-term effectiveness of atezo-bev is a critical but uncertain determinant of its cost-effectiveness. Price reduction would favorably influence cost-effectiveness, even if long-term clinical outcomes were modest. Further studies to optimize the duration and dosage of therapy are warranted.
| S-EPMC7956424 | biostudies-literature
Project description:ObjectiveWe aimed to evaluate the cost-effectiveness of atezolizumab plus bevacizumab (atezo-bev) versus sorafenib treatment in Taiwan.MethodsUsing sorafenib as the comparator, we developed a partitioned survival model to evaluate the costs and quality-adjusted life year (QALY) of the atezo-bev treatment. The time horizon of the study was 15 years, and the annual discount rate was 3%. We analyzed the incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (INMB) from the treatment effects (determined from the progression-free and overall survival outcomes of the IMbrave150 study), direct medical costs (collected and estimated from the National Health Insurance Research Database, Taiwan), and utility parameters (referred to the NICE technology appraisal guidance), as well as the deterministic sensitivity and probabilistic sensitivity.ResultsCompared with sorafenib, the incremental effectiveness of atezo-bev treatment was 1.7 QALY, with an incremental cost of USD 127,607. The ICER was USD 75,192 per QALY, which was less than the predefined willingness to pay in Taiwan.ConclusionThe combined treatment of atezo-bev is cost-effective when compared with sorafenib, which is currently the first-line treatment option for unresectable HCC in Taiwan.
| S-EPMC10663301 | biostudies-literature
Project description:ImportanceAtezolizumab plus bevacizumab as a first-line therapy for patients with unresectable or metastatic hepatocellular carcinoma has been shown to improve overall and progression-free survival compared with standard sorafenib treatment. However, because of the high cost of atezolizumab plus bevacizumab, assessment of its value by considering both efficacy and cost is needed.ObjectiveTo evaluate the cost-effectiveness of atezolizumab plus bevacizumab vs sorafenib for patients with unresectable or metastatic hepatocellular carcinoma from a US payer perspective.Design, setting, and participantsThis economic evaluation was performed from June through September 2020, with a 6-year investment time period. Hypothetical patients were male and female adults 18 years or older who had a diagnosis of locally advanced metastatic or unresectable hepatocellular carcinoma confirmed by histologic or clinical features.Main outcomes and measuresHealth care costs (adjusted to 2020 US dollars), life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) of atezolizumab plus bevacizumab vs sorafenib were examined using a partitioned survival model. One-way deterministic and probabilistic sensitivity analyses were used to examine model uncertainty. The model was also used to estimate price reductions of atezolizumab plus bevacizumab that would achieve more favorable cost-effectiveness.ResultsIn the base case analysis of a hypothetical sample of 424 patients, atezolizumab plus bevacizumab was associated with an increase of 0.623 life-years (1.840 vs 1.218 life-years) and 0.484 QALYs (1.412 vs 0.928 QALYs) and with an incremental cost of $156 210 per patient compared with sorafenib. The ICER was $322 500 per QALY (5th to 95th percentile, $149 364-$683 744 per QALY), with 0.6% and 5.1% chance of being cost-effective at willingness-to-pay thresholds of $100 000 and $150 000 per QALY, respectively. The ICER never decreased below $150 000 per QALY in the 1-way sensitivity analyses. To achieve more favorable cost-effectiveness under the thresholds of $150 000 to $100 000 per QALY, the prices of atezolizumab and bevacizumab would need to be reduced by 37% to 47%.Conclusions and relevanceIn this economic evaluation, atezolizumab plus bevacizumab was associated with clinical benefit but was not cost-effective compared with sorafenib for first-line treatment of unresectable or metastatic hepatocellular carcinoma from a US payer perspective. A substantial reduction in price for atezolizumab plus bevacizumab would be needed to achieve favorable cost-effectiveness for this new therapy.
| S-EPMC8027915 | biostudies-literature
Project description:ObjectiveAtezolizumab plus bevacizumab demonstrates a significant improvement in overall survival and progression-free survival compared with sorafenib in patients with unresectable hepatocellular carcinoma (HCC). The combined usage of these two medications could result in substantial consumption of resources, primarily due to their exceptionally high costs. The current study aims to evaluate the cost-effectiveness of atezolizumab plus bevacizumab as a first-line treatment for advanced HCC from the perspective of payers in developed and developing countries.DesignA partitioned survival model was constructed to evaluate the cost-effectiveness of atezolizumab plus bevacizumab versus sorafenib as a first-line treatment for advanced HCC. The efficacy and safety data incorporated within the model were derived from the IMbrave150 trial. Costs and utilities were extracted from published sources.InterventionsAtezolizumab plus bevacizumab versus sorafenib.Outcome measuresEstimates were calculated for costs, life-years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER) for both treatment strategies. One-way sensitivity, probabilistic sensitivity, expected value of perfect information (EVPI), subgroup and scenario analyses were conducted.ResultsThe combination therapy of atezolizumab and bevacizumab results in an additional 0.72 life-years/0.57 QALYs in the USA and 0.64 life-years/0.47 QALYs in China compared with standard sorafenib treatment, although with a significant increase in costs, yielding an average ICER of US$253 247.07/QALY in the USA and US$181 552.71/QALY in China. The probability sensitivity analysis indicated that atezolizumab plus bevacizumab demonstrated a 13.60% likelihood of cost-effectiveness in the USA, whereas this likelihood is negligible (0%) in China. The expected value of uncertainty, as quantified by the EVPI, was estimated at approximately US$3658.41/patient in the USA and US$0/patient in China. The ICER was most sensitive to the cost of subsequent treatment in the USA, and most sensitive to the cost of atezolizumab in China. In scenario analyses, the atezolizumab plus bevacizumab treatment becomes favourable when the cost of atezolizumab decreases to 67.85% and 18.45% of its original price in the USA and China, respectively.ConclusionsThe atezolizumab plus bevacizumab is unlikely to be cost-effective compared with sorafenib for patients with unresectable HCC in the context of the USA and China. The implementation of significant reductions in drug prices may render the treatment economically viable.
| S-EPMC11887288 | biostudies-literature
Project description: Not available
| S-EPMC11694292 | biostudies-literature
Project description:Background and objectiveHepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, especially in China. According to the 2021 Chinese Society of Clinical Oncology guidelines, sorafenib, lenvatinib, atezolizumab combined with bevacizumab, and sintilimab combined with bevacizumab are recommended as first-line treatment options for advanced HCC. This study provides a cost-effectiveness analysis of these treatments from the patient perspective.MethodsA partitioned survival model was established using the TreeAge 2019 software to evaluate the cost-effectiveness. The model includes three states, namely progression-free survival, progressive disease, and death. Clinical data were derived from three randomized controlled studies involving patients with advanced HCC who received the following treatment: sorafenib and lenvatinib (NCT01761266); atezolizumab in combination with bevacizumab (NCT03434379); and sintilimab in combination with bevacizumab (NCT03794440). Cost and clinical preference data were obtained from the literature and interviews with clinicians.ResultsAll compared with sorafenib therapy, lenvatinib had an incremental cost-effectiveness ratio (ICER) of US$188,625.25 per quality-adjusted life year (QALY) gained; sintilimab plus bevacizumab had an ICER of US$75,150.32 per QALY gained; and atezolizumab plus bevacizumab had an ICER of US$144,513.71 per QALY gained. The probabilistic sensitivity analysis indicated that treatment with sorafenib achieved a 100% probability of cost-effectiveness at a threshold of US$36,600/QALY. One-way sensitivity analysis revealed that the results were most sensitive to the medical insurance reimbursement ratio and drug prices.ConclusionsIn this economic evaluation, therapy with lenvatinib, sintilimab plus bevacizumab, and atezolizumab plus bevacizumab generated incremental QALYs compared with sorafenib; however, these regimens were not cost-effective at a willingness-to-pay threshold of US$36,600 per QALY. Therefore, some patients may achieve preferred economic outcomes from these three therapies by tailoring the regimen based on individual patient factors.
| S-EPMC10064722 | biostudies-literature
Project description:BackgroundLenvatinib and atezolizumab plus bevacizumab(A + B) have been used for unresectable hepatocellular carcinoma (HCC) as first-line therapy. Real-world studies comparison of efficacy and safety in these two regimens are limited, we therefore conduct this study to investigate these issues.MethodsWe retrospectively reviewed patients received lenvatinib (n = 46) and A + B (n = 46) as first-line systemic therapy for unresectable HCC in a tertiary medical center. Objective response rate (ORR), progression free survival (PFS), and overall survival (OS) were evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Inverse probability weighting (IPW) was performed for baseline clinical features balance.ResultsA total of 92 patients with median age of 63.8 year-old, 78.3% male, 85.9% viral hepatitis infected, 67.4% BCLC stage C were enrolled. The median treatment and follow-up duration were 4.7 months and 9.4 months, respectively. There was no significant difference in ORR (26.1% vs. 41.3%, p = 0.1226), PFS (5.9 vs. 5.3 months, p = 0.4066), and OS (not reached vs. not reached, p = 0.7128) between the lenvatinib and A + B groups. After IPW, the results of survival and response rate were also compared. Subgroup analysis suggested that using lenvatinib was not inferior to A + B in regards of PFS, including those with elder, Child-Pugh class B, beyond up-to-seven, or portal vein invasion VP4 patients. Among the lenvatinib treated patients, multivariate analysis showed patients elder than 65-year-old was an independent predictor associated with shorter PFS (adjust HR: 2.085[0.914-4.753], p = 0.0213). The incidence rates of adverse events were similar between two groups (76 vs. 63%, p = 0.1740). Both of two regimens had similarly few impact on liver function by comparison of baseline, third month, and sixth month albumin-bilirubin index and Child-Pugh score.ConclusionsThe efficacy and safety of lenvatinib are similar to A + B as a first-line systemic therapy for unresectable HCC.
| S-EPMC10067067 | biostudies-literature
Project description:BackgroundThe treatment of advanced hepatocellular carcinoma (HCC) with atezolizumab and bevacizumab led to significant improvements in overall survival (OS), progression-free survival (PFS), and response rate compared with sorafenib in the phase III IMbrave150 trial. The etiology of background liver disease can differ between Eastern and Western populations, leading to a potentially different impact of systemic therapies; therefore the unequal representation must be considered in the IMbrave150 trial. To provide further data on the safety and effectiveness of atezolizumab and bevacizumab, the phase IIIb AMETHISTA (Atezolizumab plus bevacizumab in METastatic HCC Italian Safety TriAl) ran in a Western (Italian) population of patients with advanced HCC. The results of the interim analysis are presented in this paper.MethodsAMETHISTA is a multicenter, phase IIIb, single-arm study evaluating the safety and effectiveness of atezolizumab and bevacizumab in an Italian population of patients with systemic treatment-naive HCC (ClinicalTrials.gov: NCT04487067). The primary objective was safety (incidence of grade 3-5 bleeding/hemorrhages). The main secondary objective was effectiveness.ResultsA total of 152 patients were enrolled and 149 were treated. At the cut-off date, the median observation time was 13.4 months (interquartile range 8.3-15.5 months). The incidence of grade 3-5 bleeding/hemorrhages was 11.4%. Besides, results of other safety endpoints were consistent with the safety profile of atezolizumab plus bevacizumab, and the underlying disease, without any new safety observation. The median OS was 18.2 months (95% confidence interval 15.4 months to not evaluable); the median PFS was 8.5 months (95% confidence interval 7.5-11.2 months).ConclusionResults from the interim analysis are consistent with data from the IMbrave150 trial, and further confirm first-line atezolizumab plus bevacizumab as a standard of care for patients with systemic treatment-naive advanced and unresectable HCC.
| S-EPMC11799967 | biostudies-literature
Project description:BackgroundIn recent years, programmed cell death protein-1 inhibitors, including sintilimab, have significantly prolonged the overall survival time of patients with unresectable or metastatic hepatocellular carcinoma (HCC); however, the cost-effectiveness of sintilimab is unclear. The aim of this study was to assess the cost-effectiveness of sintilimab plus bevacizumab biosimilar compared with lenvatinib as first-line treatment in patients with unresectable or metastatic HCC.MethodsA lifetime partitioned survival model was developed to conduct a cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar vs. lenvatinib for advanced HCC from a Chinese healthcare system perspective. The clinical and safety data were derived from two recent randomized clinical trials, the ORIENT-32 and REFLECT studies. Utility data were obtained from previous studies. Long-term direct medical costs and quality-adjusted life-years (QALYs) were predicted. Deterministic and probabilistic sensitivity analyses were performed to verify the robustness of the model.ResultsCompared with lenvatinib, combination therapy with sintilimab and bevacizumab biosimilar yielded an additional 0.493 QALYs at a higher cost ($33,102 vs. $21,037) (2021 US dollars). This resulted in a deterministic incremental cost-effectiveness ratio (ICER) of $24,462 per QALY in the base-case analysis. The ICERs were sensitive to the utility of post-progression and the cost of bevacizumab biosimilar. A lower ICER was estimated when the dose of bevacizumab biosimilar decreased from 15 mg to 7.5 mg per kilogram in the scenario analysis. In the probabilistic sensitivity analysis, the probability of being cost-effective for sintilimab treatment at willingness-to-pay (WTP) thresholds of one ($12,516) and three times the gross domestic product per capita in China ($37,547) were 11.6% and 88.6%, respectively.ConclusionSintilimab plus bevacizumab biosimilar is likely to be a cost-effective treatment option as a first-line treatment for unresectable or metastatic HCC in China when WTP threshold is over $23,650.
| S-EPMC9673291 | biostudies-literature