Model-Based Cost-Effectiveness Analysis of [18F]FDG PET/CT Early into Therapy with Immune Checkpoint Inhibitors: Tackling Pseudoprogression in Unresectable Cutaneous Melanoma Patients

Background For cutaneous melanoma patients receiving immune checkpoint inhibitors, there exists no robust and externally validated tool to differentiate actual tumour progression from pseudoprogression based upon a single imaging assessment, usually with contrast-enhanced CT. In clinically stable patients without excessive toxicity, therapy is continued to avoid premature discontinuation in patients who may demonstrate a durable response at a later time point. Ineffective therapy continuation is expected in patients with actual disease progression, which deprives these patients of the opportunity to start another therapy. Methods We estimated pseudoprogression rates in a national Dutch cutaneous melanoma population and illustrated the health economic impact of making treatment decisions based on improved insight into actual disease progression if using [ 18 F]FDG PET/CT at 8–12 weeks into therapy. This study consisted of two steps: an analysis of a response-based survival model from the Dutch Melanoma Treatment Registry to study pseudoprogression and 2-year overall survival; subsequently, an exploratory analysis of the costs and effects of [ 18 F]FDG PET/CT–guided early therapy changes using scenario modelling. Results In 514 patients with known response status at 3 and 6 months into therapy, changes in response status were determined. Pseudoprogression was indicated in 23 patients (5% of the cohort; 23/514 patients) and accounted for 20% of those initially suspected of progression at 3 months (23/115 patients). Early therapy changes in the event of actual disease progression showed health benefits but also increased lifetime costs. Given a willingness-to-pay threshold of €80,000 per QALY, early therapy changes were likely cost-effective compared with usual care. Conclusion Improved recognition of actual disease progression is clinically relevant: ineffective immunotherapy entails toxicity and unnecessary costs and delays more suitable alternatives. While [ 18 F]FDG PET/CT costs contrast sharply with therapy costs, the cost-effectiveness of [ 18 F]FDG PET/CT ultimately depends on the effect and cost of sequential therapy lines. Further empirical evidence generation is required.