A comparative review of economic evaluations for immune checkpoint inhibitors in early stage and advanced stage cancer: focusing on pembrolizumab

Introduction While immune checkpoint inhibitors (ICIs) are increasingly used in early stage cancers, how economic evaluation methods differ between early and advanced stages remains underexplored. This study aimed to compare methodological differences in economic evaluations between cancer stages and examine consistency between technology appraisals (TAs) and published articles, using pembrolizumab as an example. Methods A systematic literature review identified economic evaluations of melanoma, triple-negative breast cancer (TNBC), and renal cell carcinoma (RCC) from PubMed, Embase, and the Cochrane Library (protocol registered in PROSPERO [CRD42025646192]). Methodological characteristics and cost-effectiveness conclusions for pembrolizumab were compared between early and advanced stage articles. TAs from the National Institute for Health and Care Excellence (NICE), Canada’s Drug Agency (CDA-AMC), and Pharmaceutical Benefits Advisory Committee (PBAC) were also reviewed. Results Forty-one articles and 25 TAs were included. Economic evaluations in early stage cancers more frequently used Markov models, longer time horizons, distinct health states for recurrence and metastasis, cure assumptions, and more often concluded pembrolizumab to be cost-effective (p < 0.05). Differences between TAs and published articles were identified in time horizon and assumptions regarding treatment effect waning. Among the published articles, methodological choices related to time horizon, utility approach, and relative dose intensity (RDI) were associated with cost-effectiveness conclusions across cancer stages. Conclusion Methodological variations in economic evaluations of pembrolizumab were observed between early stage and advanced stage cancers in published articles, as well as between TAs and published articles across both stages. This study highlights the need for stage-specific modeling and clearer methodological guidance to support robust economic evaluations of ICIs in both early and advanced cancer settings.