OBJECTIVES: To evaluate the cost-effectiveness of pembrolizumab plus platinum-fluoropyrimidine vs current chemotherapies for first-line treatment of locally advanced unresectable or metastatic carcinoma of oesophagus or HER-2 negative gastro-esophageal junction adenocarcinoma in adults whose tumours express PD-L1 with a CPS≥10, from the French healthcare system perspective.

METHODS: A three-state partitioned survival model was developed to estimate costs, effects, and incremental cost-effectiveness ratio (ICER) over a 10-year time horizon. Clinical and quality of life data were derived from the Phase 3 study KEYNOTE-590. Patients’ characteristics and treatment patterns were extracted from a French prospective cohort. Survival outcomes from the trial were extrapolated using a piecewise modelling approach based on parametric survival functions. EQ-5D-5L data were converted to French population-based utilities using the French value set. Only direct medical costs were considered, based on public sources. Costs and health outcomes were discounted at 2.5% per year. ICER was calculated as cost per quality-adjusted life year (QALY) gained. Sensitivity and scenarios analyses were performed to assess robustness of results.

RESULTS: Pembrolizumab plus platinum-fluoropyrimidine brought incremental benefits vs chemotherapies of 0.94 life years gained and 0.82 life years adjusted on quality of life (QALY) per patient. This was associated with incremental costs of €89,017 per patient. The ICER of pembrolizumab in combination was estimated at €107,407/QALY vs chemotherapies. Results were mostly sensitive to parametric survival functions chosen to extrapolate overall survival; but as KEYNOTE-590 overall survival data being mature (less than 30% of patients alive at the end of follow-up period). Pembrolizumab plus platinum-fluoropyrimidine has more than 80% probability of being cost-effective beyond the willingness-to-pay (WTP) threshold of €140,000/QALY.

CONCLUSIONS: Pembrolizumab plus platinum-fluoropyrimidine improves life expectancy and appears cost-effective vs chemotherapies in this indication, assuming a WTP under €140,000/QALY.