Biomarkers aid cost-benefit analysis of head and neck cancer immunotherapy

The cost-effectiveness of the immunotherapy drug pembrolizumab for patients with locally advanced head and neck squamous cell carcinoma may depend on biomarker results in a new study.

Previously published results from the KEYNOTE-689 trial had shown that perioperative pembrolizumab improved event-free survival for head and neck squamous cell carcinoma patients.

Adding perioperative pembrolizumab to standard of care treatment, however, is both expensive and time-consuming for patients.

This latest study, published in JAMA Otolaryngology–Head & Neck Surgery, examines the KEYNOTE-689 study cohort to determine whether anticipated survival benefits outweigh the costs based on a standard threshold of what national healthcare systems are willing to pay.

The researchers compared patients with a combined positive score of 1-10 with patients with a score over 10. (Combined positive score is a measure of PD-L1 protein cells in tumor tissue, used to predict response to pembrolizumab.)

Patients with scores over 10 — those individuals measured as more likely to respond to pembrolizumab — saw an estimated 1.35 additional quality-adjusted life years at an incremental cost of $181,900 with addition of perioperative pembrolizumab to standard oncologic surgery and adjuvant therapy.

Patients with a combined positive score of 1-10 had an estimated 0.08 additional quality-adjusted life years at an incremental cost of $166,500.

The incremental cost-effectiveness ratio for the patients with combined positive scores over 10 was $134,700, versus $2,179,400 for the group with scores from 1-10.

“Perioperative pembrolizumab per the Keynote 689 protocol can add nearly a year to the standard treatment of locally advanced head and neck squamous cell carcinoma, with each cycle of the drug of costing an estimated $12,000 and an estimated additional $170-180,000 per patient,” said Pratyusha Yalamanchi, M.D., M.B.A, the study’s senior author and Clinical Assistant Professor of Otolaryngology-Head & Neck Surgery at the University of Michigan Medical School.

“These results suggest that we need more data to give both patients and providers a clearer understanding of the costs and benefits of the added therapy in their individual cases.”

The study authors note that head and neck squamous cell carcinoma is often diagnosed at advanced stages and already carries a high economic and therapeutic burden, regardless of immunotherapy treatment.

Furthermore, the length of pembrolizumab administration and its potential for side effects increases the likelihood of patients not completing the treatment course due to treatment and financial toxicity, highlighting the importance of cost-benefit analyses going forward.

“The ability of perioperative immunotherapy to improve outcomes for patients with advanced head and neck squamous cell carcinoma is incredibly exciting,” Yalamanchi said.

“We believe a stronger biomarker-stratified approach is necessary for more personalized, informed decision making for patients with locally advanced head and neck cancer.”

Additional authors: Aidan H. Coyle, B.A.; David W. Hutton, Ph.D., MSHP; Marisa R. Buchakjian, M.D., Ph.D.; Keith A. Casper, M.D.; David W. Forner, M.D., MSc; Sarah Hawley, Ph.D., M.P.H,2; Molly E. Heft Neal, M.D.; Kelly M. Malloy, M.D., M.B.A.; Michelle L. Mierzwa, M.D.; Mark E. Prince, M.D.; Jennifer L. Shah, M.D.; Paul L. Sweicicki, M.D.; Andrew G. Shuman, M.D.; Chaz L. Stucken, M.D.; Christine M. Veenstra, M.D.; Francis P. Worden, M.D.; Pratyusha Yalamanchi, M.D., M.B.A.

Tech transfer(s)/Conflict(s) of interest: Malloy reported personal fees from UpToDate outside the submitted work. Worden reported grants from Coherus, Exelexis, Loxo, PDS Biotech, Merus, Eli Lilly, Merck and Company, and Regeneron; personal fees from UpToDate, Coherus, PDS Biotech, Sun Pharma, and Eisai; is a member of the steering committee of Sun Pharma, PDS Biotech, and Exelexis; is a member of the advisory board for Exelixis, Merck and Company, Eisai, PDS Biotech, Adlai Nortye, Merus, FORE, Johnson & Johnson, and Acendo; and travel support from Sun Pharma outside the submitted work. No other disclosures were reported.

Paper cited: “Combined Positive Score and Cost-Effectiveness of Perioperative Pembrolizumab for Head and Neck Cancer,” JAMA Otolaryngology–Head & Neck Surgery. DOI: 10.1001/jamaoto.2026.2124