First-Line Atezolizumab Plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma: A Cost-Effectiveness Analysis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods
2.1. Modeling without Long-Term Outcome Data
2.2. Model Structure
2.3. Survival Estimates
2.4. Utility Estimates
2.5. Cost Estimates
2.6. Sensitivity Analyses
3. Results
3.1. Base Case Analysis
3.2. Scenario and Sensitivity Analyses
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Parameters | Base Case Value | Range | Reference | Distribution | |
---|---|---|---|---|---|
Minimum | Maximum | ||||
Clinical effectiveness [15] | |||||
HR for OS (atezo + bev vs.sorafenib) | 0.58 | 0.42 | 0.79 | [15] | Normal |
HR for PFS (atezo + bev vs. sorafenib) | 0.59 | 0.47 | 0.76 | [15] | Normal |
Weibull OS model with sorafenib | λ = 0.027, γ = 1.286 | - | - | [15] | - |
Weibull PFS model with sorafenib | λ = 0.093, γ = 1.312 | - | - | [15] | - |
Background mortality rate | Age-specific | ||||
Rate of treatment discontinuation due to AEs [15] | |||||
Atezo + Bev | 0.07 | 0.056 | 0.084 | [15] | Binomial |
Sorafenib | 0.10 | 0.08 | 0.12 | [15] | Binomial |
Proportion of patients with grade 3–4 AEs [15] | |||||
Atezo + Bev | |||||
Diarrhea | 0.018 | 0.014 | 0.022 | [15] | Binomial |
Hand–foot syndrome | 0.0 | 0.0 | 0.0 | [15] | Binomial |
Hypertension | 0.152 | 0.122 | 0.182 | [15] | Binomial |
Increased bilirubin | 0.024 | 0.019 | 0.029 | [15] | Binomial |
Sorafenib | |||||
Diarrhea | 0.051 | 0.041 | 0.061 | [15] | Binomial |
Hand–foot syndrome | 0.083 | 0.066 | 0.1 | [15] | Binomial |
Hypertension | 0.122 | 0.098 | 0.146 | [15] | Binomial |
Increased bilirubin | 0.064 | 0.051 | 0.077 | [15] | Binomial |
Patient weight, kg | 70 | 40 | 200 | [42] | Triangular |
Cost parameters, USD * | |||||
Atezolizumab (1200 mg) (fixed) (every 3 weeks) | 9419.16 | 7535.33 | 11,302.99 | [4,5] | Triangular |
Bevacizumab (15 mg/kg) (every 3 weeks) | 117.60 | 94.08 | 141.12 | [34,35,36] | Triangular |
Sorafenib (every 3 weeks) | 14,609.28 | 11,687.42 | 17,531.14 | [34,35,36] | Triangular |
Drug administration (every 3 weeks) | 435.04 | 348.03 | 522.05 | [34,35,36] | Triangular |
CT imaging (every 6 weeks) | 1543 | 1235 | 1852 | [35] | Triangular |
Other care (every week) | 174.5 | 139.6 | 209.4 | [20] | Triangular |
In-patient EOL care | 7360.16 | 6208.85 | 9313.77 | [31] | Triangular |
Post-progression therapy cost per cycle in atezo + bev | 4612.66 | 3690.13 | 5535.20 | [15] | Triangular |
Post-progression therapy cost per cycle in sorafenib | 4825.93 | 3860.74 | 5791.11 | [15] | Triangular |
Societal costs, USD * | |||||
Caregiver (every 3 weeks) | 382.21 | 305.77 | 458.65 | [43] | Triangular |
Patient time | 896.2 | 716.96 | 1075.44 | [43,44] | Triangular |
Parking/meals/travel | 329.5 | 263.6 | 395.4 | [43,45] | Triangular |
Management of Grade 3–4 AEs, USD * | |||||
Diarrhea | 88.38 | 70.70 | 106.05 | [38,39,40,41] | Triangular |
Hand–foot syndrome | 145.65 | 116.51 | 174.78 | [38,39,40,41] | Triangular |
Hypertension | 64.01 | 51.21 | 76.81 | [38,39,40,41] | Triangular |
Increased bilirubin | 0 | 0 | 0 | Estimates | Triangular |
Utilities and dis-utilities | |||||
In atezo–bev first-line therapy | 0.78 | 0.624 | 0.936 | [31] | Triangular |
In sorafenib first-line therapy | 0.78 | 0.624 | 0.936 | [21] | Triangular |
In second-line therapy | 0.68 | 0.54 | 0.82 | [21] | Triangular |
Dis-utilities | |||||
Diarrhea | −0.103 | −0.082 | −0.123 | [46] | Triangular |
Hand–foot syndrome | −0.116 | −0.093 | −0.139 | [46] | Triangular |
Hypertension | −0 | −0 | −0 | [46] | Triangular |
Increased bilirubin | −0 | −0 | −0 | [46] | Triangular |
Parameters | Atevo + Bev | Sorafenib |
---|---|---|
Treatment duration, months | Atezo: 7.4; Bev: 6.9 | 2.8 |
Cost, USD | ||
Total cost | 713,742 | 634,668 |
Clinical effectiveness, months | ||
Median PFS | 6.8 | 4.3 |
Median OS | NE | 13.2 |
Median post-progression survival | NE | 8.9 |
Utilities | ||
Utility while on first-line treatment | 0.78 | 0.78 |
AEs | −0.013 | −0.013 |
Utility at progression | 0.68 | 0.68 |
QALYs | 1.426 | 0.987 |
QALY gain | 0.440 | |
Life-years | 2.02 | 1.51 |
Incremental life-year | 0.51 | |
ICER, USD | ||
Per life-year | 155,047 (142,953–174,815) * | |
Per QALY | 179,729 (163,932–191,054) * |
Cost-Effectiveness Acceptability at WTP, % | ||||||
---|---|---|---|---|---|---|
Scenario | Life-Years | QALYs | Cost, 2020 US USD | ICER, USD/QALY | USD 100,000/ QALY | USD 150,000/ QALY |
Atezo–bev | ||||||
Base case * | 2.02 | 1.426 | 713,742 | 179,729 | 24.5 | 45.6 |
Pessimistic survival * | 1.78 | 1.227 | 727,557 | 385,857 | 4.3 | 9.7 |
Optimistic survival * | 2.48 | 1.825 | 679,811 | 53,854 | 78.1 | 92.7 |
Sorafenib | 1.51 | 0.987 | 634,668 | NA | NA | NA |
Parameters | ICER (USD /QALY) |
---|---|
Base case analysis | 179,729 |
Model Perspective | |
Third-party perspective (base case) | 179,729 |
Societal perspective | 219,058 |
Scenario analysis | |
Duration of atezo–bev | |
Until disease progression (base case) | 179,729 |
Max 24 months | 176,626 |
Max 18 months | 167,058 |
Max 12 months | 136,205 |
Max 6 months | 18,598 |
Dosage of bev (assuming a body weight of 70 kg) | |
15 mg/kg (base case) | 179,729 |
12.5 mg/kg | 167,405 |
10 mg/kg | 122,286 |
7.5 mg/kg | 107,969 |
5 mg/kg | 81,952 |
Time horizon | |
5 years (base case) | 179,729 |
10 years | 156,988 |
Lifetime | 156,710 |
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Chiang, C.-L.; Chan, S.-K.; Lee, S.-F.; Choi, H.C.-W. First-Line Atezolizumab Plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma: A Cost-Effectiveness Analysis. Cancers 2021, 13, 931. https://doi.org/10.3390/cancers13050931
Chiang C-L, Chan S-K, Lee S-F, Choi HC-W. First-Line Atezolizumab Plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma: A Cost-Effectiveness Analysis. Cancers. 2021; 13(5):931. https://doi.org/10.3390/cancers13050931
Chicago/Turabian StyleChiang, Chi-Leung, Sik-Kwan Chan, Shing-Fung Lee, and Horace Cheuk-Wai Choi. 2021. "First-Line Atezolizumab Plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma: A Cost-Effectiveness Analysis" Cancers 13, no. 5: 931. https://doi.org/10.3390/cancers13050931