Multicenter validation of an RNA-based assay to predict anti-PD-1 disease control in patients with recurrent or metastatic head and neck squamous cell carcinoma: the PREDAPT study

• DOI: 10.1136/jitc-2024-009573
• Publication Date: 2024-11-04T01:55:13Z
• Authors: Kevin C Flanagan; Jon Earls; Jeffrey Hiken; Rachel L Wellinghoff; Michelle M Ponder; Howard L McLeod; William H Westra; Vera Vavinskaya; Leisa Sutton; Ida Deichaite; Orlan K Macdonald; Karim Welaya; James Wade; Georges Azzi; Andrew W Pippas; Jennifer Slim; Bruce Bank; Xingwei Sui; Steven E Kossman; Todd D Shenkenberg; Warren L Alexander; Katharine A Price; Jessica Ley; David N Messina; Jarret I Glasscock; A Dimitrios Colevas; Ezra E W Cohen; Douglas Adkins; Eric J Duncavage
• Keywords: Male; Adult; Tumor; Squamous Cell Carcinoma of Head and Neck; Programmed Cell Death 1 Receptor; immune checkpoint inhibitor; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; tumor mutation burden (TMB); next generation sequencing (NGS); Middle Aged; Neoplasm Recurrence; Local; Head and Neck Neoplasms; Immunotherapy Biomarkers; Biomarkers, Tumor; biomarker; Humans; head and neck cancer; Female; Neoplasm Recurrence, Local; Neoplasm Metastasis; Immune Checkpoint Inhibitors; Biomarkers; RC254-282; Aged

BackgroundDespite advances in cancer care and detection, >65% of patients with squamous cell cancer of the head and neck (HNSCC) will develop recurrent and/or metastatic disease. The prognosis for these patients is poor with a 5-year overall survival of 39%. Recent treatment advances in immunotherapy, including immune checkpoint inhibitors like pembrolizumab and nivolumab, have resulted in clinical benefit in a subset of patients. There is a critical clinical need to identify patients who benefit from these antiprogrammed cell death protein 1 (anti-PD-1) immune checkpoint inhibitors.MethodsHere, we report findings from a multicenter observational study, PREDicting immunotherapy efficacy from Analysis of Pre-treatment Tumor biopsies (PREDAPT), conducted across 17 US healthcare systems. PREDAPT aimed to validate OncoPrism-HNSCC, a clinical biomarker assay predictive of disease control in patients with recurrent or metastatic HNSCC treated with anti-PD-1 immune checkpoint inhibitors as a single agent (monotherapy) and in combination with chemotherapy (chemo-immunotherapy). The test used RNA-sequencing data and machine learning models to score each patient and place them into groups of low, medium, or high.ResultsThe OncoPrism-HNSCC prediction significantly correlated with disease control in both the monotherapy cohort (n=62, p=0.004) and the chemo-immunotherapy cohort (n=50, p=0.01). OncoPrism-HNSCC also significantly predicted progression-free survival in both cohorts (p=0.015 and p=0.037, respectively). OncoPrism-HNSCC had more than threefold higher specificity than programmed death-ligand 1 combined positive score and nearly fourfold higher sensitivity than tumor mutational burden for predicting disease control.ConclusionsHere, we demonstrate the clinical validity of the OncoPrism-HNSCC assay in identifying patients with disease control in response to anti-PD-1 immune checkpoint inhibitors.Trial registration numberNCT04510129.