只有 15-20% 的复发性和/或转移性头颈鳞状细胞癌 (R/M SCCHN) 患者从纳武单抗或派姆单抗中获得长期获益。我们开发了一种循环肿瘤 DNA (ctDNA) 肿瘤不可知测定，旨在早期预测单药程序性细胞死亡 1 (PD1) 抑制剂在 R/M SCCHN 中的疗效。我们的肿瘤不可知测定包括 37 个在 R/M 中经常突变的基因SCCHN 和两个 HPV16 基因。主要终点是 ctDNA 动力学 (ΔctDNA) 与根据实体瘤 1.1 版中的反应评估标准的最佳总体反应之间的一致性。 ΔctDNA 定义为 PD1 抑制剂开始后 6-10 周 (FU1) 采集的治疗样本与治疗前血浆样本之间的平均变异等位基因频率 (VAF) 之间的差异（ΔctDNA = 平均 FU1 VAF - 平均治疗前血浆样本）在 35/44 (80%) 的治疗前血浆样本中检测到 VAF).ctDNA。 ΔctDNA 和成像反应之间的一致性为 74%。 ΔctDNA 有利组的中位无进展生存期为 8.6 个月，ΔctDNA 不利组为 2.5 个月 (p = 0.057)。 ΔctDNA 有利组和不利组的中位总生存期 (OS) 分别为 18.1 个月和 8.2 个月 (p = 0.13)。在表达 SCCHN 的 PD-L1 患者（综合阳性评分≥1）中，与 ΔctDNA 不利的患者相比，ΔctDNA 有利的患者的 OS 明显更好：中位 OS 分别为 41.5 个月和 8.4 个月 (p = 0.033)。对人乳头瘤病毒 (HPV) 阴性和 HPV 阳性 R/M SCCHN 进行 ctDNA 分析是可行的。 ctDNA 动力学在预测 PD1 抑制剂在 R/M SCCHN 中的疗效方面显示出有希望的结果。版权所有 © 2023 Elsevier Ltd。保留所有权利。

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.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).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.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.Copyright © 2023 Elsevier Ltd. All rights reserved.