Department of Head and Neck Medical Oncology, National Cancer Centre Hospital East, Kashiwa, Japan; Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Head and Neck Medical Oncology, National Cancer Centre Hospital East, Kashiwa, Japan.
Eur J Cancer. 2023 May;184:30-38. doi: 10.1016/j.ejca.2023.02.011. Epub 2023 Feb 15.
Several reports have shown that the use of proton pump inhibitors (PPIs) and antibiotics (Abx) can reduce the efficacy of immune checkpoint inhibitors in various cancers. To date, however, the association of immune checkpoint inhibitors with PPI and/or Abx in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M SCCHN) has not been reported.
We retrospectively reviewed patients with platinum-refractory R/M SCCHN treated with nivolumab from May 2017 and March 2020 in our institute. Primary sites included the oral cavity, oropharynx, hypopharynx and larynx. The relationship between prognostic parameters, such as overall survival (OS), progression-free survival (PFS), PFS2 and PFS3, and clinical factors, including PPI or Abx use, was examined, and the creation of prognostic classification was also attempted.
Of 110 patients identified, 56 patients received PPI and 24 patients received Abx within 30 days before or after the initiation of nivolumab. With a median follow-up of 17.2 months (range: 13.8-25.0), median PFS, PFS2, PFS3 and OS were 3.2, 8.1, 14.0 and 17.2 months, respectively. In univariate analysis, the use of PPI and of Abx was significantly associated with poor prognosis in all parameters (PFS, PFS2, PFS3 and OS). Median OS (hazard ratio; 95%confidence interval, p-value) by these covariates were 13.6 versus 23.8 months (1.70; 1.01-2.87, p = 0.046) for PPI and 10.0 versus 20.1 months (1.85; 1.00-3.41, p = 0.048) for Abx, respectively. Furthermore, these factors showed mutually independent adverse associations on multivariate analysis.
The use of PPI and Abx attenuated the efficacy of nivolumab in R/M SCCHN. Further prospective evaluation is warranted.
多项报告显示，质子泵抑制剂（PPIs）和抗生素（Abx）的使用会降低各种癌症中免疫检查点抑制剂的疗效。然而，迄今为止，免疫检查点抑制剂与复发性或转移性头颈部鳞状细胞癌（R/M SCCHN）患者的 PPI 和/或 Abx 的关联尚未报道。
我们回顾性分析了我院 2017 年 5 月至 2020 年 3 月期间接受纳武利尤单抗治疗的铂类耐药 R/M SCCHN 患者。原发部位包括口腔、口咽、下咽和喉。检查了总生存期（OS）、无进展生存期（PFS）、PFS2 和 PFS3 等预后参数与包括 PPI 或 Abx 使用在内的临床因素之间的关系，并尝试建立预后分类。
在确定的 110 例患者中，有 56 例患者在开始使用纳武利尤单抗前或后 30 天内使用了 PPI，有 24 例患者使用了 Abx。中位随访时间为 17.2 个月（范围：13.8-25.0），中位 PFS、PFS2、PFS3 和 OS 分别为 3.2、8.1、14.0 和 17.2 个月。单因素分析显示，PPI 和 Abx 的使用与所有参数（PFS、PFS2、PFS3 和 OS）的不良预后均显著相关。根据这些协变量，PPI 的中位 OS（风险比；95%置信区间，p 值）为 13.6 个月比 23.8 个月（1.70；1.01-2.87，p = 0.046），Abx 的中位 OS 为 10.0 个月比 20.1 个月（1.85；1.00-3.41，p = 0.048）。此外，这些因素在多变量分析中显示出相互独立的不良关联。
PPI 和 Abx 的使用会降低 R/M SCCHN 患者纳武利尤单抗的疗效。需要进一步的前瞻性评估。
