Circulating tumour DNA kinetics in recurrent/metastatic head and neck squamous cell cancer patients

• DOI: 10.1016/j.ejca.2023.04.014
• Publication Date: 2023-04-20T20:59:32Z
• Authors: Kirsty Taylor; Jinfeng Zou; Marcos Magalhaes; Marc Oliva; Anna Spreafico; Aaron R. Hansen; Simon S. McDade; Vicky M. Coyle; Mark Lawler; Elena Elimova; Scott V. Bratman; Lillian L. Siu
• Keywords: Squamous Cell Carcinoma of Head and Neck; name=Oncology; /dk/atira/pure/subjectarea/asjc/2700/2730; name=Oncology; 610; name=Cancer Research; HNSCC; 3. Good health; name=SDG 3 - Good Health and Well-being; Circulating Tumor DNA; /dk/atira/pure/subjectarea/asjc/2700/2730; Kinetics; ctDNA kinetics; Head and Neck Neoplasms; Biomarkers, Tumor; /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being; Humans; /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being; name=SDG 3 - Good Health and Well-being; Neoplasms, Squamous Cell; Neoplasm Recurrence, Local; /dk/atira/pure/subjectarea/asjc/1300/1306; Immune checkpoint blockade; /dk/atira/pure/subjectarea/asjc/1300/1306; name=Cancer Research

Immune checkpoint blockade (ICB) has become a standard of care in the treatment of recurrent/metastatic head and neck squamous cell cancer (R/M HNSCC). However, only a subset of patients benefit from treatment. Quantification of plasma circulating tumour DNA (ctDNA) levels and on-treatment kinetics may permit real-time assessment of disease burden under selective pressures of treatment.R/M HNSCC patients treated with systemic therapy, platinum-based chemotherapy (CT) or ICB, underwent serial liquid biopsy sampling. Biomarkers tested included ctDNA measured by CAncer Personalized Profiling by deep Sequencing (CAPP-Seq) and markers of host inflammation measured by neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR).Among 53 eligible patients, 16 (30%) received CT, 30 (57%) ICB [anti-PD1/L1] monotherapy and 7 (13%) combination immunotherapy (IO). Median progression-free survival (PFS) and overall survival (OS) were 2.8 months (95% CI, 1.3-4.3) and 8.2 months (95% CI, 5.6-10.8), respectively. Seven (13%) patients experienced a partial response and 21 (40%) derived clinical benefit. At baseline, median ctDNA variant allele frequency (VAF) was 4.3%. Baseline ctDNA abundance was not associated with OS (p = 0.56) nor PFS (p = 0.54). However, a change in ctDNA VAF after one cycle of treatment (ΔVAF (T1-2)) was predictive of both PFS (p< 0.01) and OS (p< 0.01). Additionally, decrease in ΔVAF identified patients with longer OS despite early radiological progression, 8.2 vs 4.6 months, hazard ratio 0.44 (95% CI, 0.19-0.87) p = 0.03. After incorporating NLR and PLR into multivariable Cox models, ctDNA ∆VAF retained an association with OS.Early dynamic changes in ctDNA abundance, after one cycle of treatment, compared to baseline predicted both OS and PFS in R/M HNSCC patients on systemic therapy.