e18829 Background: The IMbrave150 trial found that atezolizumab and bevacizumab significantly prolonged progression-free survival (PFS) and overall survival (OS) in patients with locally advanced metastatic or unresectable hepatocellular carcinoma (HCC), compared to sorafenib. However, atezolizumab and bevacizumab are costly treatments and are administered indefinitely until disease progression. Therefore, it is unclear whether atezolizumab-bevacizumab is cost-effective in this clinical setting. Methods: We constructed a partitioned survival model to compare the costs and effectiveness of atezolizumab-bevacizumab to sorafenib in advanced HCC. PFS and OS curves for each treatment strategy were derived from the IMbrave150 trial using parametric survival modeling. The utility of each health state and the costs of treatment, adverse events, and terminal care were derived from literature and Medicare fee schedules. We calculated the incremental cost-effectiveness ratio (ICER) of atezolizumab-bevacizumab from a US healthcare perspective, using a lifetime horizon, an annual discount rate of 3%, and a willingness-to-pay threshold of $150,000/quality-adjusted life year (QALY). One-way and probabilistic sensitivity analyses were performed to evaluate the robustness of model conclusions. Results: Atezolizumab-bevacizumab was associated with an incremental cost of $102,648 and an incremental effectiveness of 0.42 QALYs compared to sorafenib, leading to an ICER of $244,213/QALY (Table). The price of atezolizumab would need to be reduced by 40% (from ̃$9,400 to ̃$5,700 per dose) or the price of bevacizumab would need to be reduced by 47% (from ̃$8,400 to ̃$4,400 per dose) for atezolizumab-bevacizumab to be cost-effective compared to sorafenib. Alternatively, the price of both atezolizumab and bevacizumab would need to be simultaneously decreased by ̃21% for the combination therapy to be cost-effective. Our model was most sensitive to the hazard ratios (HR) of OS and PFS; varying the HRs across the 95% confidence interval reported in IMbrave150 (0.42-0.79) corresponded to ICERs of $137,435/QALY and $621,365/QALY, respectively. During probabilistic sensitivity analyses, >99%, 99%, and 90% of iterations produced ICERs greater than willingness-to-pay thresholds of $50,000/QALY, $100,000/QALY, and $150,000/QALY, respectively. Conclusions: Use of atezolizumab-bevacizumab for advanced HCC is unlikely to be cost-effective under current pricing. Significant price reduction of atezolizumab and/or bevacizumab would be required to reduce the ICER to a more widely acceptable value.[Table: see text]