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. 2023 Jul:188:29-38.
doi: 10.1016/j.ejca.2023.04.014. Epub 2023 Apr 20.

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

Kirsty Taylor  1 , Jinfeng Zou  2 , Marcos Magalhaes  3 , Marc Oliva  3 , Anna Spreafico  3 , Aaron R Hansen  3 , Simon S McDade  4 , Vicky M Coyle  4 , Mark Lawler  4 , Elena Elimova  3 , Scott V Bratman  5 , Lillian L Siu  6
Affiliations
Free article

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

Kirsty Taylor et al. Eur J Cancer. 2023 Jul.
Free article

Abstract

Purpose: 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.

Patients and methods: 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).

Results: 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.

Conclusions: 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.

Keywords: HNSCC; Immune checkpoint blockade; ctDNA kinetics.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KT – Nothing to declare. JZ – Nothing to declare. MM – Nothing to declare. MO reports consultant/advisory role for: Merck, EMD Serono, Transgene; Grant/Research support from (Clinical Trials): Merck, Boerhinger-Ingelheim, GlaxoSmithKline, Roche/Genentech, Bayer, Abbvie, EMD Serono, ALX Oncology, ISA Therapeutics, Ayala Therapeutics, Debiopharm; Honoraria: Merck, EMD Serono, BMS outside the submitted work. AS reports grants and personal fees from Novartis, Merck, BMS, JNJ, and Oncorus and grants from Symphogen, Roche, Northern Biologics, Regeneron, AstraZeneca MedImmune, ArrayBiopharma/Pfizer, GSK, Bayer, Surface Oncology, and Treadwell outside the submitted work. AH reports grants and other support from GSK, Merck, Eisai, and Novartis, as well as grants from MedImmune, Roche, Boehringer Ingelheim, Pfizer, Janssen, and BMS outside the submitted work. SMcD reports Co-founder/shareholder: AilseVax outside of submitted work. VC reports research grants: Astex Pharmaceuticals, Cancer Research UK, NIHR and honoraria: Servier, outside of submitted work. ML reports educational grant from Pfizer and honoraria: Pfizer, EMD Serono, Roche, Carnall Farrar outside the submitted work. EE reports receiving research funding from Bristol Myers Squibb and Zymeworks; serving as a consultant or in an advisory role for Bristol Myers Squibb, Zymeworks, and Adaptimmune; and having an immediate family member employed by Merck, outside the submitted work. SVB is inventor on patents related to cell-free DNA mutation and methylation analysis technologies that have been licensed to Roche Molecular Diagnostics and Adela, respectively. SVB is a cofounder of, has ownership in, and serves in a leadership role at Adela. LLS reports personal fees from Merck, Pfizer, Celgene, AstraZeneca, Morphosys, Roche, Loxo, Oncorus, Symphogen, Seattle Genetics, GlaxoSmithKline, Voronoi, Treadwell Therapeutics, Arvinas, Tessa, Navire, Relay Therapeutics, Rubius, Janpix, Agios, and Treadwell Therapeutics and grants from Merck, Novartis, Bristol-Myers Squibb, Pfizer, Boerhinger-Ingelheim, GlaxoSmithKline, Roche/Genentech, Karyopharm, AstraZeneca, Astellas, Bayer, AbbVie, Amgen, Symphogen, Intensity Therapeutics, Mirati, Shattucks, and Avid outside the submitted work.

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