Sintilimab Plus Bevacizumab Biosimilar Therapy Associated With Better Outcomes, Higher Costs Than Lenvatinib

According to the authors of a cost-effectiveness analysis of treatments for hepatocellular carcinoma (HCC) in China, sintilimab combined with a bevacizumab biosimilar could improve quality of life for patients, but at a higher cost than lenvatinib.

Liver cancer is the sixth most common cancer worldwide. The authors noted the incidence of liver cancer in China, where the study was conducted, is much higher than the worldwide average. HCC, the most common type of primary liver cancer, makes up 85% to 90% of liver cancer cases. Programmed cell death protein-1 inhibitors, including sintilimab, work by stimulating a tumor immune response and have “significantly prolonged the overall survival time of patients with unresectable or metastatic hepatocellular carcinoma.” However, the authors said, the cost effectiveness of sintilimab therapy for HCC is “unclear.”

Sintilimab plus bevacizumab combination therapy was approved for first-line treatment of unresectable or metastatic HCC by China’s National Medical Products Administration (NMPA) in 2021. Earlier, in 2018, the NMPA approved the oral multiple receptor tyrosine kinase inhibitor lenvatinib for treating advanced HCC. The current study compared the cost-effectiveness of sintilimab plus a bevacizumab biosimilar to lenvatinib for unresectable or metastatic HCC from a Chinese health care system perspective.

In the model, health outcomes were estimated based on clinical efficacy data from 2 recent clinical trials (ORIENT-32 and REFLECT) and indicated by quality adjusted life-years (QALYs).One important limitation of the study, according to the authors, was the indirect comparison of efficacy due to the lack of a head-to-head clinical trial comparing the 2 treatments. Treatment costs and health outcomes were combined to calculate an incremental cost-effectiveness ratio (ICER), which was adjusted to 2021 US dollars.

The authors found sintilimab plus a bevacizumab biosimilar produced an additional 0.493 QALYs at an additional cost of $12,065 compared to lenvatinib in their base case scenario. The ICER was $24,462 for each additional QALY gained. The authors explained that longer survival time in their model led to both more QALYs and higher costs for sintilimab plus a bevacizumab biosimilar. Since sintilimab therapy was associated with longer overall survival compared to lenvatinib in the referenced trials, there was a longer duration of therapy in the model and therefore higher costs.

Since the cost of the bevacizumab biosimilar accounted for large proportion (about 50%) of the cost of sintilimab combination therapy in the model, the authors analyzed reducing the dose of the bevacizumab biosimilar from 15 to 7.5 mg/kg, which they said is typical in real-world clinical practice. In this scenario, assuming the same efficacy of a lower dose of the biosimilar, the same QALYs were gained but at an additional cost of $3,715 compared to lenvatinib, less than that in the base case. In this scenario, the ICER was $7,533 per QALY. Although the cost-effectiveness was “significantly improved” compared to the base case, the authors said, the same efficacy assumption “might overestimate the results.”

In sensitivity analyses, the ICER was mainly sensitive to overall survival associated with sintilimab treatment, the cost of the bevacizumab biosimilar, and the cost of subsequent treatment in the sintilimab combination therapy group. Based on variations in these parameters, the ICER varied from $14,304 to $34,113 per QALY.

The authors based willingness-to-pay (WTP) thresholds on the gross domestic product (GDP) per capita of China in 2021 ($12,516). Their results suggested the probabilities of sintilimab therapy being cost-effective were 12.6%, 56%, and 89% at WTP thresholds of 1, 2, and 3 times the GDP per capita of China. When WTP was more than $23,650, sintilimab plus bevacizumab had a higher probability of being cost-effective than lenvatinib.

Reference

Zhou T, Wang X, Cao Y, et al. Cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar compared with lenvatinib as the first-line treatment of unresectable or metastatic hepatocellular carcinoma. BMC Health Serv Res. 2022;22(1):1367. doi: 0.1186/s12913-022-08661-4