Ανάλυση κόστους - αποτελεσματικότητας του συνδυασμού Εnfortumab Vedotin + Pembrolizumab ως θεραπεία πρώτης γραμμής σε ασθενείς με προχωρημένο ή μεταστατικό ουροθηλιακό καρκίνο

Τριμπούνα, Ναταλία

Cost-effectiveness analysis of the combination of Enfortumab Vedotin + Pembrolizumab as first-line therapy in patients with advanced or metastatic urothelial carcinoma

Master Thesis

Author

Τριμπούνα, Ναταλία

Date

2026

Abstract

Urothelial carcinoma is one of the most common malignancies of the urinary tract, with the bladder being the primary site of disease. It represents a major public health challenge due to its high morbidity, substantial mortality, and considerable economic burden on healthcare systems. For many years, platinum-based chemotherapy was considered the standard first-line treatment for patients with locally advanced or metastatic urothelial carcinoma. However, the introduction of immunotherapies and targeted therapies has significantly changed the therapeutic landscape and improved treatment outcomes. The EV-302/KEYNOTE-A39 trial identified the combination of Enfortumab Vedotin and Pembrolizumab as a highly effective first-line treatment for patients with advanced or metastatic urothelial carcinoma. Compared with standard platinum-based chemotherapy, patients receiving the combination therapy achieved markedly better clinical outcomes. Median overall survival reached 31.5 months, compared with 16.1 months in the chemotherapy group, corresponding to a 53% reduction in the risk of death (HR = 0.47). Similarly, median progressionfree survival was 12.5 months versus 6.3 months, representing a 55% reduction in the risk of disease progression or death (HR = 0.45). In addition, the objective response rate was 67.7% in the combination group compared with 44.4% in the chemotherapy group, while complete responses were observed in 29.1% and 12.5% of patients, respectively. Enfortumab Vedotin is an antibody–drug conjugate that targets Nectin-4, a protein highly expressed in urothelial carcinoma cells, enabling the selective delivery of a cytotoxic agent directly to tumor cells. Pembrolizumab is a monoclonal antibody directed against the programmed cell death protein-1 (PD-1) receptor, enhancing the body's antitumor immune response by restoring T-cell activity. Together, these agents exert complementary mechanisms of action that translate into superior clinical outcomes compared with conventional chemotherapy. Objective: The aim of this study was to evaluate the cost-effectiveness of Enfortumab Vedotin plus Pembrolizumab compared with standard chemotherapy as first-line treatment for adults with locally advanced or metastatic urothelial carcinoma. The economic evaluation was conducted from the perspective of the Greek National Health System to determine whether the additional clinical benefits of the combination therapy justify its higher acquisition cost. Methods: A three-state Partitioned Survival Model (PSM) was developed, including progression-free survival (PFS), progressed disease (PD), and death. Clinical efficacy data were obtained from the EV-302/KEYNOTE-A39 trial, whereas cost inputs, health-state utilities, adverse event management costs, and healthcare resource utilization were derived from published international and Greek literature. The model simulated patient outcomes over a 180-month time horizon using monthly cycles. Future costs and health outcomes were discounted at an annual rate of 3.5%. Effectiveness was assessed in terms of life-years (LYs), quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). In addition, a one-way sensitivity analysis was performed to evaluate the robustness of the model and identify the parameters with the greatest impact on the results. Results: The base-case analysis showed that treatment with Enfortumab Vedotin plus Pembrolizumab resulted in higher overall costs than standard chemotherapy but also generated greater health benefits. Specifically, the combination therapy increased total treatment costs by €91,360 compared with chemotherapy. At the same time, it provided an additional 1.10 life-years and 0.89 quality-adjusted life-years (QALYs) per patient. The resulting incremental costeffectiveness ratio (ICER) was estimated at €102,198 per QALY gained. Sensitivity analysis demonstrated that drug acquisition cost was the parameter with the greatest influence on the ICER, whereas changes in the discount rate and adverse event management costs had only a limited impact on the overall findings. Conclusions: Enfortumab Vedotin plus Pembrolizumab represents a clinically effective firstline treatment for advanced or metastatic urothelial carcinoma, although its economic value remains sensitive to drug pricing and key modelling assumptions. Whether the therapy can be considered cost-effective depends largely on the willingness-to-pay threshold adopted and the reimbursement policies of the Greek healthcare system. The findings of this study may provide useful evidence for healthcare decision-makers when assessing reimbursement strategies and the incorporation of innovative anticancer therapies into routine clinical practice.

Postgraduate Studies Programme

Οικονομικά και Διοίκηση της Υγείας

Department

Σχολή Οικονομικών, Επιχειρηματικών και Διεθνών Σπουδών. Τμήμα Οικονομικής Επιστήμης

Number of pages

Language

Greek

URI

https://dione.lib.unipi.gr/xmlui/handle/unipi/19653

Collections

Τμήμα Οικονομικής Επιστήμης

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Except where otherwise noted, this item's license is described as
Αναφορά Δημιουργού-Μη Εμπορική Χρήση-Όχι Παράγωγα Έργα 3.0 Ελλάδα