Treating unresectable hepatocellular carcinoma (uHCC) is challenging. Clinical trials have shown that Single Tremelimumab Regular Interval Durvalumab (STRIDE) offers clinical benefits as a first-line treatment for uHCC, but its cost effectiveness remains unknown in the USA. We aimed to assess the cost effectiveness of STRIDE (tremelimumab plus durvalumab) versus sorafenib and durvalumab monotherapy as the first-line treatment for uHCC in the USA. A partitioned survival model was constructed to assess the cost effectiveness of STRIDE compared to sorafenib and durvalumab monotherapy as the first-line treatment for uHCC from the US societal perspective. The time horizon was 48 months with 1-month cycles. Seven parametric survival functions replicated survival curves from clinical trials, with the best-fitting model used to calculate survival probabilities. Costs, health utilities, and adverse events were included, with quality-adjusted life-years (QALYs) as the primary effectiveness measure. Both costs and effectiveness were discounted at 3%. In the base-case analysis, the incremental cost-effectiveness ratio was compared to a willingness-to-pay threshold of $150,000 per QALY gained. Deterministic and probabilistic sensitivity analyses were conducted to examine the uncertainty of the model. In the base-case analysis, STRIDE was cost effective compared to sorafenib, with an incremental cost-effectiveness ratio of $97,995.51 per QALY gained, based on a willingness-to-pay threshold of $150,000 per QALY gained. However, STRIDE was not cost effective compared to durvalumab monotherapy at the same threshold, with an incremental cost-effectiveness ratio of $754,408.92 per QALY gained. Deterministic sensitivity analyses were consistent with the base-case analysis. A probabilistic sensitivity analysis indicated that STRIDE was more likely to be cost effective than sorafenib and durvalumab monotherapy when the willingness-to-pay exceeded $101,000 and $713,000, respectively. The STRIDE regimen appears to be cost effective compared to sorafenib but not compared to durvalumab for first-line uHCC treatment in the USA. However, durvalumab has not yet been approved for uHCC in the USA. Future research should focus on long-term data and economic evaluations of other recommended biologics.
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