Table_2_EGFR Mutation and 11q13 Amplification Are Potential Predictive Biomarkers for Immunotherapy in Head and Neck Squamous Cell Carcinoma.docx

BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most common malignant cancers. The treatment of HNSCC remains challenging despite recent progress in targeted therapies and immunotherapy. Research on predictive biomarkers in clinical settings is urgently needed.
MethodsNext-generation sequencing analysis was performed on tumor samples from 121 patients with recurrent or metastatic HNSCC underwent sequencing analysis. Clinicopathological information was collected, and the clinical outcomes were assessed. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and cox regression model was used to conduct multivariate analysis. Fisher’s exact tests were used to calculate clinical benefit. A p value of less than 0.05 was designated as significant (p < 0.05).
ResultsChromosome 11q13 amplification (CCND1, FGF3, FGF4, and FGF19) and EGFR mutations were significantly associated with decreased PFS and no clinical benefits after treatment with a programmed death 1 (PD-1) inhibitor. The same results were found in the combined positive score (CPS) ≥ 1 subgroup. In patients who were treated with an EGFR antibody instead of a PD-1 inhibitor, a significant difference in PFS and clinical benefits was only observed between patients with CPS ≥ 1 and CPS < 1.
ConclusionChromosome 11q13 amplification and EGFR mutations were negatively correlated with anti-PD-1 therapy. These markers may serve as potential predictive biomarkers to identify patients for whom immunotherapy may be unsuitable.

背景：头颈部鳞状细胞癌（Head and neck squamous cell carcinoma, HNSCC）是最为常见的恶性肿瘤之一。尽管靶向治疗与免疫治疗领域近年取得进展，头颈部鳞状细胞癌的临床治疗仍颇具挑战，临床亟需可用于疗效预测的生物标志物。
方法：本研究对121例复发或转移性头颈部鳞状细胞癌患者的肿瘤样本开展二代测序（next-generation sequencing, NGS）分析。研究收集了患者的临床病理信息，并对临床结局进行评估：采用Kaplan-Meier法估算无进展生存期（progression-free survival, PFS），使用Cox回归模型开展多因素分析；采用Fisher精确检验计算临床获益情况，以p值<0.05作为统计学显著性阈值。
结果：染色体11q13区域扩增（涵盖CCND1、FGF3、FGF4及FGF19基因）与表皮生长因子受体（Epidermal Growth Factor Receptor, EGFR）突变，均与患者接受程序性死亡受体1（programmed death 1, PD-1）抑制剂治疗后无进展生存期缩短、未获得临床获益显著相关。上述结果在联合阳性评分（combined positive score, CPS）≥1的亚组中同样成立。在接受EGFR抗体而非PD-1抑制剂治疗的患者中，仅在CPS≥1与CPS<1的患者间观察到无进展生存期及临床获益存在显著差异。
结论：染色体11q13区域扩增与EGFR突变，均与抗PD-1治疗疗效呈负相关。上述标志物或可作为潜在的预测性生物标志物，用于筛选不适于免疫治疗的患者。