Tumour-agnostic plasma assay for circulating tumour DNA predicts outcome in recurrent and/or metastatic squamous cell carcinoma of the head and neck treated with a PD-1 inhibitor.
- Resource Type
- Academic Journal
- Authors
- Honoré N; Pôle Oncologie, Institut de Recherche Clinique et Expérimentale, Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 10, 1200 Brussels, Belgium; Department of Medical Oncology, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Brussels, Belgium.; van der Elst A; Pôle Oncologie, Institut de Recherche Clinique et Expérimentale, Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 10, 1200 Brussels, Belgium; Department of Medical Oncology, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Brussels, Belgium.; Dietz A; Department of Radiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.; van Marcke C; Pôle Oncologie, Institut de Recherche Clinique et Expérimentale, Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 10, 1200 Brussels, Belgium; Department of Medical Oncology, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Brussels, Belgium.; Helaers R; Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain (UCLouvain), Brussels, Belgium.; Mendola A; Pôle Oncologie, Institut de Recherche Clinique et Expérimentale, Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 10, 1200 Brussels, Belgium.; Dahou H; Pôle Oncologie, Institut de Recherche Clinique et Expérimentale, Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 10, 1200 Brussels, Belgium.; Marbaix E; Department of Pathology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.; Poncin R; Department of Medical Oncology, Cliniques Saint-Pierre, Ottignies, Belgium.; Seront E; Department of Medical Oncology, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Department of Medical Oncology, Jolimont Hospital, La Louviere, Belgium.; Schmitz S; Pôle Oncologie, Institut de Recherche Clinique et Expérimentale, Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 10, 1200 Brussels, Belgium; Department of ENT and Maxillo-facial Surgery, Cliniques Universitaires Saint-Luc, Brussels, Belgium.; Limaye N; Genetics of Autoimmune Diseases and Cancer, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.; Galot R; Pôle Oncologie, Institut de Recherche Clinique et Expérimentale, Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 10, 1200 Brussels, Belgium; Department of Medical Oncology, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Brussels, Belgium.; Machiels JP; Pôle Oncologie, Institut de Recherche Clinique et Expérimentale, Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 10, 1200 Brussels, Belgium; Department of Medical Oncology, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Brussels, Belgium. Electronic address: jean-pascal.machiels@saintluc.uclouvain.be.
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- Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 9005373 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0852 (Electronic) Linking ISSN: 09598049 NLM ISO Abbreviation: Eur J Cancer Subsets: MEDLINE
- Subject
- Language
- English
Background: Only 15-20% of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) patients derive long-term benefit from nivolumab or pembrolizumab. We developed a circulating tumour DNA (ctDNA) tumour-agnostic assay aimed at the early prediction of single agent programmed cell death 1 (PD1) inhibitor efficacy in R/M SCCHN.
Patients and Methods: Our tumour-agnostic assay included 37 genes frequently mutated in R/M SCCHN and two HPV16 genes. Primary endpoint was the concordance between ctDNA kinetics (ΔctDNA) and the best overall response according to Response Evaluation Criteria in Solid Tumors version 1.1. ΔctDNA was defined as the difference in mean variant allele frequency (VAF) between the on-treatment sample harvested 6-10 weeks (FU1) after PD1 inhibitor initiation and the pre-treatment plasma sample (ΔctDNA = mean FU1 VAF - mean pre-treatment VAF).
Results: ctDNA was detected in 35/44 (80%) of the pre-treatment plasma samples. The concordance between ΔctDNA and imaging response was observed in 74%. Median progression-free survival was 8.6 months in the favourable ΔctDNA group and 2.5 months in the unfavourable ΔctDNA group (p = 0.057). Median overall survival (OS) was 18.1 and 8.2 months in the favourable and unfavourable ΔctDNA groups, respectively (p = 0.13). In patients with PD-L1 expressing SCCHN (Combined Positive Score ≥1), OS was significantly better in patients with favourable ΔctDNA compared with patients with unfavourable ΔctDNA: median OS was 41.5 and 8.4 months (p = 0.033), respectively.
Conclusions: Tumour-agnostic ctDNA analysis for human papillomavirus (HPV)-negative and HPV-positive R/M SCCHN is feasible. ctDNA kinetics show promising results in predicting the efficacy of PD1 inhibitors in R/M SCCHN.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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