Cost-effectiveness Analysis in the New Era of Treatment Strategies in Metastatic Urothelial Carcinoma Based on Checkmate-901 and EV302/Keynote-A39

Abstract

Background and objective

Metastatic urothelial carcinoma (mUCa) ranks as the costliest cancer to treat per patient due to frequent interventions and expensive follow-ups. Investigating first-line therapies, combinations such as enfortumab vedotin + pembrolizumab (EV + P) and gemcitabine/cisplatin + nivolumab exhibit significant overall survival benefits compared with the standard treatment (SoC; gemcitabine/cisplatin). Here, we conducted a cost-effectiveness analysis for mUCa.

Methods

We developed a Markov model from a payer perspective, filtering clinical data from the phase 3 Checkmate-901 and EV302/Keynote-A39 trials. Monte Carlo simulation was used to identify the optimal treatment from a socioeconomic perspective in Germany and the USA. Finally, we compared the incremental cost-effectiveness ratio (ICER) of each modality at different willingness-to-pay (WTP) thresholds.

Key findings and limitations

At a lifetime horizon, SoC, gemcitabine/cisplatin + nivolumab, and EV + P were associated with average costs of €163 424 (USA: $458 006), €206 853 (USA: $597 802), and €401 170 (USA: $1 228 455), and gained quality-adjusted life years (QALYs) of 1.21, 1.71, and 2.31, respectively. The ICERs of the newer strategies were €87 340 (USA: $281 142; gemcitabine/cisplatin + nivolumab) and €216 140 (USA: $700 448; EV + P). At a commonly used WTP threshold of €/$100 000, gemcitabine/cisplatin + nivolumab would be the optimal strategy in Germany, while EV + P would require a price reduction of 46% (USA: 82%) to be cost effective.

Conclusions and clinical implications

QALYs nearly double with EV + P compared with the current SoC; yet, current costs may not be justified from a strict socioeconomic perspective. Despite its lower oncological benefit, gemcitabine/cisplatin + nivolumab should be considered for first-line therapy due to favorable cost effectiveness, especially in Europe. Establishing individual risk factors is essential for optimizing therapeutic response and treatment costs in the future.

Patient summary

This report presents a cost-effectiveness analysis of emerging treatment options for metastatic urothelial carcinoma. The combination of enfortumab vedotin + pembrolizumab emerged as the most effective treatment; however, it also proved to be the costliest. From a purely socioeconomic standpoint, the combination of gemcitabine/cisplatin and nivolumab represents a cost-effective alternative at least in Germany.