Impact of prophylactic dexamethasone on the efficacy of immune checkpoint inhibitors plus platinum-based chemotherapy in patients with advanced Non-Squamous Non-Small-Cell lung cancer
Impact of prophylactic dexamethasone on the efficacy of immune checkpoint inhibitors plus platinum-based chemotherapy in patients with advanced Non-Squamous Non-Small-Cell lung cancer
复制标题
DOI：
10.1016/j.intimp.2023.111138
复制
发表时间：
2023-11-08
影响因子：
5.6
通讯作者：
Hong，Shaodong
中科院分区：
文献类型：
--
作者：
Yu，Hui;Chen，Jingyu;Hong，Shaodong
背景：在接受程序性细胞死亡-1（PD-1）轴阻断治疗的非小细胞肺癌（NSCLC）患者中，基线皮质类固醇暴露与较差的临床结局相关。地塞米松是一种有效的皮质类固醇，用于预防化疗相关不良事件（CAAE）。目的由于地塞米松具有免疫抑制作用，本研究试图阐明其对非鳞状NSCLC患者免疫治疗加化疗疗效的影响。方法本研究回顾性分析了254例接受一线PD治疗的晚期非鳞状NSCLC患者的病历，1通路抑制剂和铂类化疗在三个学术机构。计算每个化疗周期预防性应用地塞米松的平均剂量。根据地塞米松剂量将患者分为三组：高d（≥24 mg）、中d（12-24 mg）和低d（<12 mg）。使用斯皮尔曼等级相关性评估地塞米松剂量与无进展生存期（PFS）之间的相关性。采用Logistic回归分析地塞米松剂量与免疫相关不良反应（irAE）发生率的相关性。结果地塞米松预防剂量与PFS无显著相关性（斯皮尔曼's rho =-0.103，P = 0.098）。单变量[风险比（HR）Low-d/High-d，1.00;P= 0.997; HR Moderate-d/High-d，0.85;P= 0.438]和多变量（HR Low-d/High-d，0.71;P= 0.174; HR Moderate-d/High-d，0.87;P= 0.512）分析结果显示地塞米松与PFS之间无显著相关性。地塞米松对客观缓解率、疾病控制率和总生存期无显著影响。irAE的毒性特征在所有三个groups.ConclusionThe本研究的结果表明，使用预防性地塞米松没有对PD-1阻断治疗和化疗治疗的非鳞状NSCLC患者的临床结局产生不良影响。对于接受联合免疫治疗和化疗的患者，应推荐常规使用地塞米松预防CAAE。
BackgroundBaseline corticosteroids exposure is associated with inferior clinical outcomes in patients with non-small-cell lung cancer (NSCLC) treated with programmed cell death-1 (PD-1) axis blockade. Dexamethasone is a potent corticosteroid used in the prevention of chemotherapy-associated adverse events (CAAEs).ObjectiveSince dexamethasone has immunosuppressive properties, this study attempted to elucidate its effects on the efficacy of immunotherapy plus chemotherapy in patients with non-squamous NSCLC.MethodsThe study retrospectively analyzed the medical records of 254 advanced non-squamous NSCLC patients who received front-line treatment with a PD-1 pathway inhibitor and platinum-based chemotherapy at three academic institutions. The average dosage of prophylactic dexamethasone per chemotherapy cycle was calculated. Patients were divided into three groups based on the dose of dexamethasone: High-d (≥24 mg), Moderate-d (12–24 mg), and Low-d (<12 mg). Spearman's rank correlation was used to assess the correlation between the dosage of dexamethasone and progression-free survival (PFS). Logistic regression was used to assess the correlation between dexamethasone dosage and the occurrence of immune related adverse effects (irAE). Univariate and multivariate Cox proportional hazards regression models were used to analyze the differences in survival among the different dexamethasone dosage groups.ResultThe dosage of prophylactic dexamethasone was not significantly correlated with PFS (Spearman’s rho = -0.103,P= 0.098). Results from the univariate [hazard ratio (HR)Low-d/High-d, 1.00;P= 0.997; HRModerate-d/High-d, 0.85;P= 0.438] and multivariate (HRLow-d/High-d, 0.71;P= 0.174; HRModerate-d/High-d, 0.87;P= 0.512) analyses showed no significant association between dexamethasone and PFS. Dexamethasone did not have significant effect on the objective response rate, disease control rate or overall survival. The toxicity profiles of irAE were similar across all three groups.ConclusionThe results of this study suggest that the use of prophylactic dexamethasone does not have an adverse effect on the clinical outcomes of non-squamous NSCLC patients treated with PD-1 blockade therapy and chemotherapy. Routine use of dexamethasone for preventing CAAEs should be recommended for patients undergoing combined immunotherapy and chemotherapy.