TOPLINE:

In a cost-effectiveness analysis from a US healthcare payer perspective, nivolumab plus ipilimumab vs lenvatinib or sorafenib modestly improved survival but yielded an incremental cost-effectiveness ratio (ICER) of $200,408.61 per quality‐adjusted life year (QALY), exceeding the conventional US willingness-to-pay thresholds. The findings suggested that the combination of nivolumab plus ipilimumab was unlikely to be cost-effective as first-line therapy for unresectable hepatocellular carcinoma (HCC). However, extending the dosing interval or reducing the combined price of the drugs might render the regimen economically viable.

METHODOLOGY:

• HCC has a high mortality rate and a rising incidence in the US, imposing substantial healthcare costs and financial hardships on patients. Although the use of immune checkpoint inhibitors has improved outcomes in patients with unresectable HCC, their high prices raise concerns about value. After the CheckMate 9DW trial reported improved overall survival with nivolumab plus ipilimumab vs lenvatinib or sorafenib, this study evaluated whether the combination represented good value from a US healthcare payer perspective via a cost-effectiveness analysis.
• Researchers included 668 patients with unresectable HCC who had histologically confirmed disease and no prior systemic treatment, at least one measurable untreated lesion per response evaluation criteria in solid tumors version 1.1, Child-Pugh scores of 5 or 6, and Eastern Cooperative Oncology Group performance status of 0 or 1.
• The nivolumab plus ipilimumab group received intravenous nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) every 3 weeks for up to four doses, followed by nivolumab monotherapy (480 mg administered intravenously every 4 weeks). The comparison group received either oral lenvatinib (8 mg/d for body weight < 60 kg or 12 mg/d for body weight ≥ 60 kg) or oral sorafenib (400 mg twice daily).
• Researchers used a partitioned survival model with three health states (progression-free survival, progressed disease, and death), deriving survival proportions using areas under the curve from the CheckMate 9DW trial; the model cycle length was 21 days, and a 10-year time horizon was used for the base case analysis.
• Probabilistic sensitivity and multiple scenario analyses were performed. The primary outcomes included total costs, QALYs, life years, and ICERs associated with nivolumab plus ipilimumab vs lenvatinib or sorafenib therapy.

TAKEAWAY:

• Nivolumab plus ipilimumab produced an incremental gain of 0.66 QALYs at an additional cost of $132,651.81, resulting in an ICER of $200,408.61 per QALY, which exceeded the US willingness-to-pay thresholds. These findings indicated that the nivolumab plus ipilimumab regimen was unlikely to be cost‐effective as first‐line therapy for unresectable HCC.
• In probabilistic sensitivity analysis comparing nivolumab plus ipilimumab with lenvatinib or sorafenib, the regimen was cost-effective in 20% and 4.6% of scenarios at willingness-to-pay thresholds of $100,000 and $150,000 per QALY, respectively.
• In the scenario analysis, using wholesale acquisition cost pricing lowered the ICER to $149,287 per QALY, accounting for drug wastage increased the ICER (rounding-up method, $263,828.90 per QALY; dose adjustment method, $221,097.95 per QALY), and switching maintenance nivolumab to subcutaneous formulation had minimal effect (ICER, $204,883 per QALY). However, extending nivolumab’s maintenance dosing to 480 mg every 8 weeks reduced the ICER to $82,201.58 per QALY, making the regimen cost-effective.
• Overall, reducing the combined price of nivolumab and ipilimumab to 89.2% of the base price increased the probability of cost-effectiveness to 50%.

IN PRACTICE:

“Our findings suggest that nivolumab plus ipilimumab is unlikely to be cost-effective within US [willingness-to-pay] thresholds of $100,000/QALY and $150,000/QALY,” the authors of the study wrote, noting that “achieving cost-effectiveness may require price reductions (particularly for ipilimumab) or exploration of alternative dosing strategies.”

SOURCE:

The study, led by Jiefeng Luo, PhD, and Zhengxiong Li, MSc, Fudan University Shanghai Cancer Center, Shanghai, and School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou, China, was published online in Cancer.

LIMITATIONS:

Because of limited post-progression data in the CheckMate 9DW trial, investigators simplified the proportions and options for subsequent treatment, potentially underrepresenting real-world complexity. The study lacked head-to-head comparative data with other immune checkpoint inhibitor-based regimens widely used as first-line treatments for unresectable HCC. Additionally, health utility values were sourced from external studies rather than the CheckMate 9DW trial, potentially affecting generalizability due to differences in baseline characteristics and cultural preferences across populations.

DISCLOSURES:

No external funding was used in this study. The authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.