Combined Positive Score and Cost-Effectiveness of Perioperative Pembrolizumab for Head and Neck Cancer

The KEYNOTE-689 trial demonstrated improved event-free survival with the addition of perioperative pembrolizumab to standard of care for patients with locally advanced head and neck squamous cell carcinoma (HNSCC), yet the cost-effectiveness remains unknown.

To evaluate the cost-effectiveness of the KEYNOTE-689 perioperative pembrolizumab protocol.

A partitioned survival model simulated the KEYNOTE-689 trial cohort with 3 mutually exclusive health states: event-free survival, disease progression, and death. Model inputs included Healthcare Cost and Utilization Project-derived and US Centers for Medicare & Medicaid Services-derived costs for drug acquisition (pembrolizumab and cisplatin), administration, surgery, radiation therapy, supportive care, management of serious adverse events, and disease progression.

KEYNOTE-689 Kaplan-Meier survival estimates were digitized and data for the combined positive score (CPS) of 1 to 10 subgroup were derived from the reported CPS of 1 or greater and CPS of 10 or greater subgroups. Quality-adjusted life-year (QALY) values for different health states were sourced from published literature, with the US population preference-weighting algorithm applied to EuroQol 5-Dimension 3-Level health questionnaire data from the CheckMate 141 trial. The primary outcome was the incremental cost-effectiveness ratio (ICER) results stratified by programmed cell death 1 ligand 1 (PD-L1) combined positive score (CPS of 1 to 10 vs greater than 10). A probabilistic sensitivity analysis (PSA) was performed to evaluate parameter uncertainty.

Subgroup analyses based on PD-L1 expression yielded divergent results. In the CPS greater than 10 cohort, perioperative pembrolizumab was cost-effective, producing approximately 1.35 additional QALYs at an incremental cost of $181 900, resulting in an ICER of $134 700. PSA showed a 57% probability that the pembrolizumab strategy was cost-effective at a $150 000 willingness-to-pay (WTP) threshold. In the CPS of 1 to 10 cohort, perioperative pembrolizumab resulted in approximately 0.08 additional QALYs at an incremental cost of $166 500, for an ICER of $2 179 400, with the PSA demonstrating an 11% probability of cost-effectiveness at a $150 000 WTP threshold.

In this economic evaluation, addition of perioperative pembrolizumab to standard treatment for locally advanced HNSCC may represent a cost-effective intervention for patients with a PD-L1 CPS greater than 10 if KEYNOTE-689 data are replicable in clinical practice. Perioperative pembrolizumab is not a cost-effective strategy for patients with a CPS less than 10 based on current data. Biomarker stratification may inform the value-based integration of immunotherapy among patients with HNSCC.