Cost-effectiveness of Pembrolizumab As Second-Line Therapy for the Treatment of Locally Advanced or Metastatic Urothelial Carcinoma in the United States.

e16010 Background: Pembrolizumab is approved by the US Food and Drug Administration for the treatment of locally advanced or metastatic urothelial carcinoma (mUC) following platinum-based chemotherapy, based on results from KEYNOTE-045. In this randomized phase 3 trial, pembrolizumab significantly prolonged overall survival (OS) vs. chemotherapy in mUC patients (cut-off: Oct 26, 2017). The current analysis evaluates the cost-effectiveness of pembrolizumab vs. standard-of-care chemotherapy (docetaxel or paclitaxel) as second-line (2L) treatment for mUC, from a US payer perspective. Methods: We developed a partitioned-survival model to measure the costs and effectiveness over a 20-year time horizon to capture long-term costs and benefits from the treatments. Clinical efficacy, time on treatment, safety and utility data were derived from KEYNOTE-045. OS and progression-free survival were extrapolated beyond the trial period using piecewise models, i.e., Kaplan-Meier data followed by parametric function. Costs (in 2018 $US) for drug acquisition/administration, disease monitoring, adverse events management and terminal care were included. Costs and outcomes were discounted at 3% per year. Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the results. Results: Pembrolizumab resulted in a mean gain of 1.33 life years (LYs) and 1.14 quality-adjusted life-years (QALYs) at an incremental cost of $103,861 vs. chemotherapy. The incremental cost-effectiveness ratios were $91,103/QALY and $78,254/LY. Key drivers of cost-effectiveness were extrapolation methods for OS data, time horizon and utility values. Pembrolizumab had a 72% or 100% probability of being cost-effective vs. chemotherapy at a $100,000 or $150,000 willingness-to-pay threshold, respectively. Conclusions: Pembrolizumab appears to be cost-effective vs. docetaxel or paclitaxel monotherapy as 2L mUC therapy when accounting for durable survival seen in a subset of patients receiving pembrolizumab. The model was established based on robust estimates, with key clinical endpoints directly drawn or derived from patient level data in KEYNOTE-045.