Dataset Information

Cost-effectiveness of Atezolizumab Plus Bevacizumab vs Sorafenib for Patients With Unresectable or Metastatic Hepatocellular Carcinoma.

ABSTRACT:

Importance

Atezolizumab 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.

Objective

To 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 participants

This 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 measures

Health 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.

Results

In 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 relevance

In 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.

SUBMITTER: Zhang X

PROVIDER: S-EPMC8027915 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

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.

Project description:IntroductionAtezolizumab plus bevacizumab significantly improved overall survival (OS) and progression-free survival (PFS) versus sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in IMbrave150. Efficacy and safety data from the Chinese subpopulation are reported.MethodsIMbrave150, a global, randomized, open-label, phase 3 study in patients with systemic treatment-naive unresectable HCC, included an extension phase that enrolled additional patients from mainland China. Patients were randomized (2:1) to receive intravenous atezolizumab 1,200 mg plus bevacizumab 15 mg/kg once every 3 weeks or sorafenib 400 mg twice a day until unacceptable toxicity or loss of clinical benefit. Co-primary endpoints were OS and independent review facility-assessed PFS per Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat population.ResultsOf 194 Chinese patients enrolled from April 16, 2018, to April 8, 2019 (137 in the global study and 57 in the China extension phase), 133 received atezolizumab plus bevacizumab and 61 received sorafenib. At the data cutoff (August 29, 2019), the stratified hazard ratio for OS was 0.44 (95% CI, 0.25-0.76) and for PFS was 0.60 (95% CI, 0.40-0.90). The respective median OS and PFS with atezolizumab plus bevacizumab were not reached (NR; 95% CI, 13.5 months to NR) and 5.7 months (95% CI, 4.2-8.3) versus 11.4 months (95% CI, 6.7 to NR) and 3.2 months (95% CI, 2.6-4.8) with sorafenib. Grade 3-4 adverse events (AEs) occurred in 78 of 132 (59.1%) atezolizumab plus bevacizumab-treated and 27 of 58 (46.6%) sorafenib-treated patients. The most common grade 3-4 AE with atezolizumab plus bevacizumab was hypertension, occurring in 15.2% of patients; however, other high-grade AEs were infrequent.ConclusionClinically meaningful improvements in OS and PFS observed with atezolizumab plus bevacizumab versus sorafenib suggest that atezolizumab plus bevacizumab may become a practice-changing treatment for Chinese patients with unresectable HCC.

Project description:IntroductionThe efficacy of systemic first-line treatments in older adults with unresectable hepatocellular carcinoma (HCC) has not been well-studied. We compared the safety and efficacy of atezolizumab plus bevacizumab versus sorafenib as a first-line treatment in younger versus older patients with unresectable HCC.MethodsThis global, phase 3, open-label, randomized clinical trial (IMbrave150) recruited patients aged ≥18 years with locally advanced metastatic or unresectable HCC, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and Child-Pugh class A liver function who had not previously received systemic therapy for liver cancer. Patients received either 1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks or 400 mg sorafenib orally twice daily until loss of clinical benefit or unacceptable toxicity. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary outcomes were the incidence of adverse events and time to deterioration of patient-reported outcomes (PROs). This subgroup analysis evaluated safety and efficacy endpoints in patients <65 years, ≥65 to <75 years, and ≥75 years.ResultsOf 501 patients, 165 patients were randomized to sorafenib and 336 were randomized to atezolizumab plus bevacizumab (175 patients <65 years; 106 patients ≥65 to <75 years; 55 patients ≥75 years). Across all age groups, patients receiving atezolizumab plus bevacizumab had longer median OS (<65: 18.0 vs. 12.2 months [HR, 0.57; 95% CI: 0.40-0.82]; ≥65 to <75: 19.4 vs. 14.9 months [HR, 0.80; 95% CI: 0.52-1.23]; ≥75: 24.0 vs. 18.0 months [HR, 0.72, 95% CI: 0.37-1.41]) and PFS than those receiving sorafenib. Time to deterioration for multiple PROs was delayed for patients receiving atezolizumab plus bevacizumab, including older adults. There were no clinically meaningful differences in toxicity between age groups.ConclusionAtezolizumab plus bevacizumab is safe and effective in adults <65, ≥65 to <75, and ≥75. Treatment was well-tolerated even in elderly patients.