OBJECTIVES: To assess the cost-effectiveness of pembrolizumab versus paclitaxel or docetaxel monotherapy in patients with locally advanced or metastatic urothelial cancer, who have previously received treatment with platinum-containing chemotherapy in England.

METHODS: A three-state partition survival model was developed, projecting costs and outcomes over a 35-year time horizon with a one-week cycle. As per the NICE reference case, costs and outcomes were discounted with a 3.5% annual discount rate. Clinical efficacy, adverse events and quality of life data were derived from KEYNOTE-045; a phase III randomised trial of pembrolizumab versus investigator’s choice of chemotherapy. Due to the use of subsequent immunotherapy regimens in the chemotherapy arm, the observed overall survival (OS) was confounded, and as such adjusted using the two-stage adjustment method. Within the model, OS was extrapolated using a piece-wise approach, utilising Kaplan-Meier data (data cut-off date 18th January 2017) until week 40, and the log-normal distribution for the remainder of the time horizon. Alternative extrapolation cut-off and parametric functions were tested in scenario analyses. Quality-adjusted life years (QALYs) were estimated using time-to-death utilities derived from EQ-5D data collected in the KEYNOTE-045 trial. Costs were applied from the NHS perspective. To assess model uncertainty, probabilistic and deterministic sensitivity analyses were performed.

RESULTS: The use of pembrolizumab as modelled above demonstrates an increase in life expectancy by 1.18 years for patients, corresponding to a gain of 0.90 QALYs versus chemotherapy. The base case incremental cost-effectiveness ratio (ICER) is £41,004 (confidential discount included). The results are sensitive to assumptions around extrapolation of OS and methodology of utility estimates.

CONCLUSIONS: Using a willingness to pay threshold of £50,000 per QALY gained, as per the NICE end-of-life criteria, pembrolizumab represents a cost-effective treatment option for NHS England when compared to docetaxel or paclitaxel monotherapy.