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

J Immunother Cancer. 2024 Nov 3;12(11):e009573. doi: 10.1136/jitc-2024-009573.

Abstract

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.

Keywords: biomarker; head and neck cancer; immune checkpoint inhibitor; next generation sequencing (NGS); tumor mutation burden (TMB).

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Female
  • Head and Neck Neoplasms* / drug therapy
  • Head and Neck Neoplasms* / genetics
  • Head and Neck Neoplasms* / pathology
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / drug therapy
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Squamous Cell Carcinoma of Head and Neck* / drug therapy
  • Squamous Cell Carcinoma of Head and Neck* / genetics

Substances

  • Immune Checkpoint Inhibitors
  • Programmed Cell Death 1 Receptor
  • PDCD1 protein, human
  • Biomarkers, Tumor

Associated data

  • ClinicalTrials.gov/NCT04510129