Abstract
Background and PurposeThe KEYNOTE-181 study demonstrated that pembrolizumab for advanced or metastatic esophageal cancer in patients with programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 10 had a survival advantage and better tolerability than chemotherapy. However, at the same time, pembrolizumab places an economic burden on patients. This study assessed the cost-effectiveness of pembrolizumab based on the KEYNOTE181 study.Materials and MethodsA three-state Markov model [progression-free survival (PFS), progressive disease (PD), and death] based on data from the KEYNOTE-181 study was used to estimate the incremental cost-effectiveness ratio (ICER) of pembrolizumab versus chemotherapy for advanced or metastatic esophageal cancer. The model evaluates the outcomes from the Chinese society's perspective. Costs, quality-adjusted life-years (QALYs), and the ICER in terms of 2021 US$ per QALY gained, were calculated. one-way and probabilistic sensitivity analyses were performed to evaluate the model robustness.ResultsCompared with chemotherapy, pembrolizumab increased costs by $37,201.68, while gaining 0.23 QALYs, resulting in an ICER of $163,165.26 per QALY in patients with PD-L1 CPS ≥ 10. The ICER is $202,708.62 per QALY and $163,643.19 per QALY in the total population and patients with esophageal squamous cell carcinoma, respectively. The ICER was much higher than the commonly accepted willingness-to-pay threshold ($11,105.8 per QALY). One-way and sensitivity analyses showed that the costs of pembrolizumab and the utility of PD were the crucial factors in determining the ICER, and probabilistic sensitivity analyses demonstrated pembrolizumab is unlikely to be cost-effective at a willingness-to-pay threshold of $11,105.8 per QALY. The result was robust across sensitivity analyses.ConclusionPembrolizumab is not a cost-effective treatment option for the second-line treatment of esophageal cancer from the perspective of Chinese society.
Highlights
Esophageal cancer is a highly lethal malignancy, with 604,100 new cases and 544,076 deaths in 2020 [1]
One-way and sensitivity analyses showed that the costs of pembrolizumab and the utility of progressive disease (PD) were the crucial factors in determining the incremental cost-effectiveness ratio (ICER), and probabilistic sensitivity analyses demonstrated pembrolizumab is unlikely to be costeffective at a willingness-to-pay threshold of $11,105.8 per quality-adjusted life-years (QALYs)
The ICER of the pembrolizumab group compared with the chemotherapy group was $202,708.62 per QALY, which was almost 6 times higher than the willingness to pay (WTP) threshold for cost-effectiveness ($11,105.8 per QALY in China)
Summary
Esophageal cancer is a highly lethal malignancy, with 604,100 new cases and 544,076 deaths in 2020 [1]. The prognosis of esophageal cancer is improving but remains poor, with an overall 5-year survival rate of about 20% [4, 5]. Targeted drugs have demonstrated efficacy in many cancers, no targeted drugs are approved for esophageal squamous cell carcinoma. Until immune checkpoint inhibitors were approved for esophageal cancer, the treatment after first-line was limited. The goal of second-line treatment for metastatic esophageal cancer was to palliate symptoms. Unresectable, locally advanced, or metastatic esophageal cancer are not curable. Esophageal cancer contributed to a massive burden on public health care systems in China [7]. The KEYNOTE-181 study demonstrated that pembrolizumab for advanced or metastatic esophageal cancer in patients with programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 10 had a survival advantage and better tolerability than chemotherapy. This study assessed the cost-effectiveness of pembrolizumab based on the KEYNOTE181 study
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