OBJECTIVES

: To estimate the cost-effectiveness of pembrolizumab monotherapy and in combination with chemotherapy for the first-line treatment of recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients whose tumor expressed programmed death-ligand 1 (PD-L1) at combined positive score (CPS) ≥1 in France.

METHODS

: A partitioned survival model was developed to predict the lifetime costs and health outcomes of treatment with pembrolizumab either as monotherapy or in combination with platinum+5-FU versus cetuximab+platinum+5-FU (EXTREME regimen). Progression-free survival (PFS) and overall survival (OS) from the KEYNOTE-048 trial were extrapolated over a 10-year time horizon using a piecewise modelling approach based on parametric functions (cut-off points of 52 weeks for PFS and 80 weeks for OS), independently fitted for each treatment arm. Time on treatment for first-line treatment was modelled using the Kaplan-Meier data only. Utilities were derived from KEYNOTE-048 and converted to French population-based utility values using a published algorithm. Only direct medical costs were considered, based on public sources. Results’ uncertainty was explored through sensitivity analyses around the model’s main assumptions.

RESULTS

: In patients with CPS≥1, pembrolizumab in combination was associated with an incremental gain of +1.18 life-years (LYs) and +0.78 quality-adjusted life-years (QALYs) at an extra-cost of €58,962, representing an incremental cost-effectiveness ratio (ICER) of €75,443/QALY vs. EXTREME. Pembrolizumab monotherapy led to an incremental gain of 0.46 LYs and 0.33 QALYs at an extra-cost of €26,547, resulting in an ICER of 80,736€/QALY vs. EXTREME. Results were most sensitive to survival extrapolations, discount rate and body surface area. The willingness-to-pay threshold should reach €110,000/QALY and €94,000/QALY to have >80% probability of being cost-effective, respectively for pembrolizumab monotherapy and pembrolizumab in combination vs. EXTREME.

CONCLUSIONS

: In the first-line treatment of R/M HNSCC patients with PD-L1 expression at CPS≥1, pembrolizumab extends patients’ survival at acceptable ICERs for oncologic treatments in France.