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免疫检查点抑制剂在治疗前中性粒细胞与淋巴细胞比值低且体能状态良好的食管癌患者中疗效最佳。

Maximum Efficacy of Immune Checkpoint Inhibitors Occurs in Esophageal Cancer Patients With a Low Neutrophil-to-Lymphocyte Ratio and Good Performance Status Prior to Treatment.

机构信息

Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.

Division of Medical Pharmacology, Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan.

出版信息

Anticancer Res. 2024 Aug;44(8):3397-3407. doi: 10.21873/anticanres.17160.

Abstract

BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) play an important role in the treatment of esophageal cancer (EC). However, few patients achieve long-term survival, and some patients develop serious immune-related adverse events (irAEs). Reliable predictive biomarkers of efficacy and safety need to be established in order to improve efficacy. We retrospectively analyzed the outcomes of nivolumab monotherapy on EC at Showa University, Department of Medicine, to identify biomarkers and characteristics of patients who benefit from ICI monotherapy.

PATIENTS AND METHODS

Eighty-six patients with EC who received nivolumab monotherapy were included in the present study. Patient characteristics, efficacy, and safety were analyzed. A multivariable analysis evaluated the correlation among overall survival (OS), progression-free survival (PFS), best overall response (BOR), irAEs, and the following variables: sex, age, performance status (PS), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP) level, albumin level, and body-mass index before treatment.

RESULTS

Median PFS was 3.1 months, and median OS was 9.0 months. In multivariable analysis, pretreatment PS, NLR, and sex were significantly correlated with OS and PFS. NLR <3.3 predicted longer survival (median OS 17.5 vs. 6.4 months for NLR ≥3.3; p<0.001). Median OS was 10.6 months for PS 0-1 and 1.3 months for PS 2-3 (p<0.001). NLR remained significantly predictive in the PS 0-1 group. The development of irAEs was significantly associated with increased OS and PFS.

CONCLUSION

Patients with low NLR and good PS before treatment may maximize the benefits of ICIs. A low NLR may be an indicator of higher immunocompetence for anti-tumor immunity, suggesting that NLR may be a convenient predictive biomarker in daily practice.

摘要

背景/目的:免疫检查点抑制剂(ICIs)在食管癌(EC)的治疗中发挥着重要作用。然而,只有少数患者能够获得长期生存,且部分患者出现严重的免疫相关不良事件(irAEs)。为了提高疗效,需要建立可靠的疗效和安全性预测生物标志物。本研究回顾性分析了昭和大学医学部采用纳武利尤单抗单药治疗 EC 的结果,旨在确定能够从 ICI 单药治疗中获益的患者的生物标志物和特征。

患者和方法

本研究纳入了 86 例接受纳武利尤单抗单药治疗的 EC 患者。分析了患者特征、疗效和安全性。多变量分析评估了总生存期(OS)、无进展生存期(PFS)、最佳总体反应(BOR)、irAEs 与以下变量之间的相关性:性别、年龄、体力状态(PS)、中性粒细胞与淋巴细胞比值(NLR)、C 反应蛋白(CRP)水平、白蛋白水平和治疗前的体重指数。

结果

中位 PFS 为 3.1 个月,中位 OS 为 9.0 个月。多变量分析显示,治疗前 PS、NLR 和性别与 OS 和 PFS 显著相关。NLR <3.3 预测生存期更长(NLR ≥3.3 时的中位 OS 为 17.5 个月 vs. 6.4 个月;p<0.001)。PS 0-1 时的中位 OS 为 10.6 个月,PS 2-3 时为 1.3 个月(p<0.001)。在 PS 0-1 组中,NLR 仍然具有显著的预测价值。irAEs 的发生与 OS 和 PFS 的延长显著相关。

结论

治疗前 NLR 较低且 PS 较好的患者可能会最大限度地受益于 ICIs。治疗前 NLR 较低可能提示抗肿瘤免疫的免疫能力较高,表明 NLR 可能是日常实践中一种方便的预测生物标志物。

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