Evaluating cost-effectiveness in the evolving treatment landscape for metastatic urothelial carcinoma.

695 Background: Metastatic urothelial carcinoma (mUCa) is the most expensive cancer to treat on a per-patient basis, largely due to the need for frequent interventions and costly follow-up care. In examining first-line therapies, combinations such as enfortumab-vedotin plus pembrolizumab (EV + P) and gemcitabine/cisplatin plus nivolumab show substantial overall survival advantages over the standard treatment (SoC) of gemcitabine/cisplatin. This study presents a cost-effectiveness analysis for mUCa. Methods: We developed a Markov model from a payer's perspective, utilizing clinical data derived from the Phase III Checkmate-901 and EV302/Keynote-A39 trials. To identify the optimal treatment from a socioeconomic standpoint, we employed Monte Carlo simulation, focusing on Germany and the United States (US). Subsequently, we compared the incremental cost-effectiveness ratio (ICER) for each treatment modality across various willingness-to-pay (WTP) thresholds. Results: At a lifetime horizon, SoC, gemcitabine/cisplatin plus nivolumab and EV + P were associated with average costs of €163,424 (US: $458,006), €206,853 (US: $597,802), and €401,170 (US: $1,228,455), respectively, while achieving QALYs of 1.21, 1.71, and 2.31, respectively. The ICERs for the newer treatment strategies were €87,340 (US: $281,142) for gemcitabine/cisplatin plus nivolumab and €216,140 (US: $700,448) for EV + P. At a commonly accepted WTP threshold of €/$100,000, gemcitabine/cisplatin plus nivolumab emerged as the optimal strategy in Germany, while EV + P would necessitate a price reduction of 46% (US: 82%) to achieve cost-effectiveness. Conclusions: QALYs nearly double with the combination of EV + P compared to the current SoC; however, the associated costs may not be justifiable from a strict socioeconomic perspective. Despite offering lower oncological benefits, gemcitabine/cisplatin plus nivolumab should be considered for first-line therapy due to its favorable cost-effectiveness, particularly in Europe. Furthermore, identifying individual risk factors is crucial for optimizing therapeutic responses and managing treatment costs in the future.