Hori Tomoki, Yamamoto Kazuhiro, Ito Takefumi, Ikushima Shigeki, Omura Tomohiro, Yano Ikuko
Department of Pharmacy, Nara Prefecture General Medical Center, 2-897-5 Shichijo-Nishimachi, Nara, 630-8581, Japan.
Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-Cho, Chuo-Ku, Kobe, 650-0017, Japan.
Int J Clin Oncol. 2025 Sep 2. doi: 10.1007/s10147-025-02859-2.
The neutrophil-to-lymphocyte ratio (NLR) at the initiation of immune checkpoint inhibitor (ICI) therapy is a known predictor of prognosis. Proton pump inhibitors (PPIs) reportedly attenuate the therapeutic efficacy of ICIs. However, the attenuation effects are not consistently observed across all patients. This study aimed to evaluate whether NLR serves as a stratification factor to determine the impact of PPI on the efficacy of ICI.
This retrospective study was conducted in patients with NSCLC treated with ICI monotherapy. Patients were stratified into two groups (higher NLR (≥ 4) and lower NLR (< 4)). PPI use was defined as the administration of PPIs within 30 days before or after ICI initiation. The primary outcome was progression-free survival (PFS) and the secondary outcome was overall survival (OS).
Among the 132 patients included, PPI users exhibited significantly shorter median PFS and OS than non-PPI users. In the higher NLR group (n = 61), PPI users had a markedly shorter PFS and OS than non-PPI users (median PFS: 1.6 vs. 8.2 months; p < 0.01, median OS: 3.3 vs. 19.6 months; p = 0.015). Conversely, in the lower NLR group (n = 71), no significant difference in PFS and OS was observed between PPI users and non-PPI users (median PFS: 2.8 vs. 7.3 months, p = 0.83, median OS: 17.6 vs. 24.4 months, p = 0.40).
NLR may be a significant stratification factor for evaluating the impact of PPI on PFS and OS in patients with NSCLC undergoing ICI monotherapy.
免疫检查点抑制剂（ICI）治疗开始时的中性粒细胞与淋巴细胞比值（NLR）是已知的预后预测指标。据报道，质子泵抑制剂（PPI）会减弱ICI的治疗效果。然而，并非所有患者都能持续观察到这种减弱效应。本研究旨在评估NLR是否可作为分层因素来确定PPI对ICI疗效的影响。
本回顾性研究纳入接受ICI单药治疗的非小细胞肺癌（NSCLC）患者。患者被分为两组（NLR较高（≥4）和NLR较低（<4））。PPI使用定义为在ICI开始前或后30天内使用PPI。主要结局是无进展生存期（PFS），次要结局是总生存期（OS）。
在纳入的132例患者中，使用PPI的患者的中位PFS和OS显著短于未使用PPI的患者。在NLR较高的组（n = 61）中，使用PPI的患者的PFS和OS明显短于未使用PPI的患者（中位PFS：1.6个月对8.2个月；p < 0.01，中位OS：3.3个月对19.6个月；p = 0.015）。相反，在NLR较低的组（n = 71）中，使用PPI的患者和未使用PPI的患者在PFS和OS方面未观察到显著差异（中位PFS：2.8个月对7.3个月，p = 0.83，中位OS：17.6个月对24.4个月，p = 0.40）。
NLR可能是评估PPI对接受ICI单药治疗的NSCLC患者的PFS和OS影响的重要分层因素。
