糖皮质激素对免疫检查点抑制剂治疗非小细胞肺癌临床效果的影响

Impact of glucocorticoids on clinical efficacy of immune checkpoint inhibitors in non-small cell lung cancer

  • 摘要:
    目的 评估糖皮质激素(GC)对免疫检查点抑制剂(ICI)治疗晚期非小细胞肺癌(NSCLC)临床效果的影响。
    方法 回顾性分析扬州大学附属医院接受ICI治疗的131例晚期NSCLC患者的临床资料,根据患者在ICI治疗前后3个月内是否使用GC类药物(≥10 mg/d泼尼松或等效GC)分为GC组(n=79)与Non-GC组(n=52)。GC组根据GC用途不同分为非肿瘤症状相关组、肿瘤症状相关组、免疫相关不良事件(irAEs)组及化疗前预处理组。分析GC使用与患者一般临床特征的相关性。采用Kaplan-Meier生存曲线分析GC使用对患者总生存期(OS)及无进展生存期(PFS)的影响。采用单因素和多因素Cox风险比例回归模型分析GC使用是否为NSCLC患者预后的影响因素。
    结果 卡方检验分析显示,GC使用与患者年龄(χ2=0.180,P=0.672)、性别(χ2=3.179,P=0.075)、吸烟(χ2=0.579,P=0.447)、病理类型(χ2=0.628,P=0.428)、美国东部肿瘤协作组(ECOG)评分(χ2=0.074,P=0.785)、治疗线数(χ2=1.853,P=0.173)无相关性,与治疗策略有相关性(χ2=3.998,P=0.046)。GC组的OS及PFS短于Non-GC组,差异有统计学意义(P < 0.05)。多因素Cox回归分析显示,使用GC是晚期NSCLC免疫治疗患者OS(HR=1.82,P=0.026)和PFS(HR=1.76,P=0.012)的独立影响因素。亚组分析表明,相比于非肿瘤相关症状、irAEs、预处理,肿瘤相关症状患者采用GC治疗的OS(P=0.006)及PFS(P=0.011)较短。多因素Cox回归分析表明,GC用于治疗肿瘤相关症状是影响ICI治疗晚期NSCLC患者OS(P=0.001)及PFS(P=0.005)的独立危险因素。
    结论 GC的使用与ICI治疗晚期NSCLC的临床疗效呈负相关,特别是GC用于肿瘤相关症状时ICI疗效明显降低,因此接受ICI治疗的晚期NSCLC患者应慎重使用GC。

     

    Abstract:
    Objective To evaluate the impact of glucocorticoids (GC) on the clinical efficacy of immune checkpoint inhibitors (ICI) in treating non-small cell lung cancer (NSCLC).
    Methods The clinical data of 131 patients with advanced NSCLC who received ICI treatment in the Affiliated Hospital of Yangzhou University were retrospectively analyzed. They were divided into GC group (n=79) and non-GC group (n=52) according to whether they used GC (≥ 10 mg/d prednisone or equivalent GC) within 3 months before and after ICI treatment or not. The GC group was divided into four subgroups according to the following indications: non-cancer indications group, cancer indications group, immune related adverse events (irAEs) group and pre-chemotherapy treatment group. The correlation between GC usage and the clinical characteristics of patients was analyzed. The Kaplan-Meier survival curve was used to analyze the impact of GC use on overall survival (OS) and progression-free survival (PFS). The univariate and multivariate analysis based on Cox hazard proportional regression models were used to identify whether GC use was a prognostic factor.
    Results No significant correlations were found between GC use and age (χ2=0.180, P=0.672), gender (χ2=3.179, P=0.075), smoking (χ2=0.579, P=0.447), pathological type (χ2=0.628, P=0.428), the score of United States Eastern Collaborative Group(ECOG) (χ2=0.074, P=0.785) score and treatment lines (χ2=1.853, P=0.173), while it was correlated with treatment strategies (χ2=3.998, P=0.046). The OS and PFS of the GC group were shorter when compared with the non-GC group, and the differences were statistically significant (P < 0.05). The multivariate analysis showed that GC use was an independent influencing factor for OS (HR=1.82, P=0.026) and PFS (HR=1.76, P=0.012). The subgroup analysis demonstrated that patients receiving GC for cancer related indications had shorter OS (P=0.006) and PFS (P=0.011) than those receiving GC for non-cancer indications, irAEs, and pre-chemotherapy treatment. The multivariate analysis showed that GC use for cancer related indications was an independent risk factor for OS (P=0.001) and PFS (P=0.005).
    Conclusion The GC use is negatively correlated with the clinical efficacy of ICI in treating patients with advanced NSCLC, especially for those receiving GC for cancer-related indications. GC should be used cautiously in ICI-treated NSCLC patients.

     

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