Ανάλυση κόστους-αποτελεσματικότητας του pembrolizumab σε συνδυασμό με χημειοθεραπεία έναντι χημειοθεραπείας μόνο ως πρώτης γραμμής θεραπεία σε ασθενείς με προχωρημένο καρκίνο οισοφάγου: Ανάλυση από την οπτική του ελληνικού συστήματος υγείας βάσει της κλινικής μελέτης KEYNOTE-590

Σιώζιος, Ευάγγελος

Cost-effectiveness analysis of pembrolizumab in combination with chemotherapy versus chemotherapy only as first-line treatment in patients with advanced esophageal cancer: an analysis from the perspective of the Greek healthcare system based on the KEYNOTE-590 clinical trial

Master Thesis

Author

Σιώζιος, Ευάγγελος

Date

2026

Abstract

Oesophageal cancer is one of the most aggressive forms of malignancy, with a particularly poor prognosis in the advanced and metastatic setting, where median survival under standard chemotherapy remains well below one year. It ranks as the eleventh most common cancer worldwide and the seventh leading cause of cancer-related death, while in Greece the incidence is relatively low, with 252 new cases and 228 deaths recorded in 2022. According to the findings of the randomized phase III clinical trial KEYNOTE-590, the combination of pembrolizumab with chemotherapy (cisplatin and 5-fluorouracil) demonstrated statistically significant improvements in both overall survival and progression-free survival compared to chemotherapy alone. Median overall survival was 12.4 months in the combination arm versus 9.8 months in the control arm, while in the subgroup of patients with high PD-L1 expression (CPS≥10) the clinical benefit was even more pronounced, with a median survival of 13.5 versus 9.4 months. Pembrolizumab is a humanized IgG4 monoclonal antibody that binds to the PD-L1 receptor, preventing the deactivation of T-lymphocytes by cancer cells. In this way, the ability of the immune system to recognize and destroy the tumour is enhanced. Scope: The present study aims to assess the cost and effectiveness of the combination of pembrolizumab with chemotherapy versus chemotherapy alone, as first-line treatment in adult patients with locally advanced or metastatic oesophageal cancer. The analysis was conducted from the perspective of the Greek National Health System (NHS). Methods: For the conduct of the cost-effectiveness analysis, a three-state Partitioned Survival Model was developed, comprising the health states: "progression-free survival (PFS)," "progressed disease (PD)," and "death." The population was modelled based on data from the KEYNOTE-590 trial, while clinical data were extracted from published Kaplan-Meier curves through digitization and extrapolated over a 20-year time horizon using a Log-Normal distribution. Costs were sourced from official Greek databases (Galinos, KEN, and Government Gazette). A discount rate of 3.5% per annum was applied to both costs and QALYs. The analysis was performed across three subgroups: all randomized patients, patients with oesophageal squamous cell carcinoma, and patients with PD-L1 CPS≥10. Results: In the overall population, the combination of pembrolizumab with chemotherapy yielded 1.13 QALYs versus 0.74 QALYs for chemotherapy alone, with an incremental cost of €70,499. The ICER amounted to €179,121/QALY. In the PD-L1 CPS≥10 subgroup, the incremental clinical benefit was 0.655 QALYs, resulting in a more favourable ICER of €120,806/QALY. Sensitivity analysis revealed that the price of the drug exerts the greatest influence on the ICER, while a 50% price reduction would render the treatment marginally cost-effective in the CPS≥10 subgroup (ICER ≈€69,842/QALY). Conclusions: According to the findings of the analysis, the combination of pembrolizumab with chemotherapy as first-line treatment in patients with advanced oesophageal cancer, while offering meaningful clinical benefit, does not appear to be cost-effective at current prices for the Greek National Health System. Achieving cost-effectiveness would require a substantial reduction in the price of the drug through negotiation, as well as a focus on the subgroup of patients with high PD-L1 expression (CPS≥10), where the clinical benefit is clearly greater.

Postgraduate Studies Programme

Οικονομικά και Διοίκηση της Υγείας

Department

Σχολή Οικονομικών, Επιχειρηματικών και Διεθνών Σπουδών. Τμήμα Οικονομικής Επιστήμης

Number of pages

112

Language

Greek

URI

https://dione.lib.unipi.gr/xmlui/handle/unipi/19641

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