TY - JOUR
T1 - 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
T2 - The PREDAPT study
AU - Flanagan, Kevin C.
AU - Earls, Jon
AU - Hiken, Jeffrey
AU - Wellinghoff, Rachel L.
AU - Ponder, Michelle M.
AU - McLeod, Howard L.
AU - Westra, William H.
AU - Vavinskaya, Vera
AU - Sutton, Leisa
AU - Deichaite, Ida
AU - Macdonald, Orlan K.
AU - Welaya, Karim
AU - Wade, James
AU - Azzi, Georges
AU - Pippas, Andrew W.
AU - Slim, Jennifer
AU - Bank, Bruce
AU - Sui, Xingwei
AU - Kossman, Steven E.
AU - Shenkenberg, Todd D.
AU - Alexander, Warren L.
AU - Price, Katharine A.
AU - Ley, Jessica
AU - Messina, David N.
AU - Glasscock, Jarret I.
AU - Colevas, A. Dimitrios
AU - Cohen, Ezra E.W.
AU - Adkins, Douglas
AU - Duncavage, Eric J.
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2024/11/3
Y1 - 2024/11/3
N2 - Background Despite 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. Methods Here, 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. Results The 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. Conclusions Here, 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 number NCT04510129.
AB - Background Despite 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. Methods Here, 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. Results The 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. Conclusions Here, 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 number NCT04510129.
KW - biomarker
KW - head and neck cancer
KW - immune checkpoint inhibitor
KW - next generation sequencing (NGS)
KW - tumor mutation burden (TMB)
UR - http://www.scopus.com/inward/record.url?scp=85208473351&partnerID=8YFLogxK
U2 - 10.1136/jitc-2024-009573
DO - 10.1136/jitc-2024-009573
M3 - Article
C2 - 39489541
AN - SCOPUS:85208473351
SN - 2051-1426
VL - 12
JO - Journal for ImmunoTherapy of Cancer
JF - Journal for ImmunoTherapy of Cancer
IS - 11
M1 - e009573
ER -