Importance: Immune checkpoint inhibitors have been approved for use as a second-line therapy for hepatocellular carcinoma (HCC) in patients who previously received sorafenib. Pembrolizumab has shown substantial antitumor activity and a favorable toxicity profile as a second-line treatment of HCC. However, considering the high cost of pembrolizumab, there is a need to assess its value by considering both the clinical efficacy and cost.
Objective: To evaluate the cost-effectiveness of pembrolizumab vs placebo as second-line therapy in patients with HCC from the US payer perspective.
Design, setting, and participants: A Markov model was developed to compare the lifetime cost and efficacy of pembrolizumab as a second-line treatment of HCC with those of placebo using outcome data from the KEYNOTE-240 randomized placebo-controlled trial, which included 413 patients with advanced HCC previously treated with sorafenib and randomized patients to receive pembrolizumab plus best supportive care or placebo plus best supportive care in a 2:1 ratio.
Main outcomes and measures: Life-years, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER) were estimated at a willingness-to-pay threshold of $150 000 per QALY. One-way and probabilistic sensitivity analyses were performed to account for the parameter of uncertainty. A cost-threshold analysis was also performed. The study was conducted from January 31 to July 29, 2020.
Results: The base-case model found that treatment with pembrolizumab was associated with increased overall cost by $47 057 and improved effectiveness by 0.138 QALYs compared with placebo, leading to an ICER of $340 409 per QALY. The model was most sensitive to the hazard ratio of overall survival (range, 0.61-1.00), health utility of placebo (range, 0.59-0.93), price of pembrolizumab (range, $5531-$8297), and price of postprogression therapies (range, $5596-$7944 for pembrolizumab and $4770-$7156 for placebo). The ICER of pembrolizumab was larger than $150 000 per QALY in most of the sensitivity and subgroup analyses. The price of pembrolizumab needed to be reduced by 57.7% to $2925 per cycle to achieve cost-effectiveness.
Conclusions and relevance: The findings of this cost-effectiveness analysis suggest that, at its current price, pembrolizumab is not a cost-effective second-line therapy for HCC in the US, with a willingness-to-pay threshold of $150 000 per QALY.