State Key Laboratory of Oncology in South China, Guangzhou, Guangdong 510060, China; Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, Guangdong 510060, China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China.
Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Int Immunopharmacol. 2023 Dec;125(Pt B):111138. doi: 10.1016/j.intimp.2023.111138. Epub 2023 Nov 8.
Baseline 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).
Since dexamethasone has immunosuppressive properties, this study attempted to elucidate its effects on the efficacy of immunotherapy plus chemotherapy in patients with non-squamous NSCLC.
The 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.
The 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), 1.00; P = 0.997; HR, 0.85; P = 0.438] and multivariate (HR, 0.71; P = 0.174; HR, 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.
The 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.
基线皮质类固醇暴露与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）患者的临床结局较差有关。地塞米松是一种用于预防化疗相关不良事件（CAAEs）的强效皮质类固醇。
由于地塞米松具有免疫抑制特性，因此本研究试图阐明其对非鳞状 NSCLC 患者免疫治疗联合化疗疗效的影响。
本研究回顾性分析了在三家学术机构接受 PD-1 通路抑制剂联合铂类化疗一线治疗的 254 例晚期非鳞状 NSCLC 患者的病历。计算每个化疗周期中预防性地塞米松的平均剂量。根据地塞米松的剂量将患者分为三组：高剂量（≥24mg）、中剂量（12-24mg）和低剂量（<12mg）。采用 Spearman 秩相关评估地塞米松剂量与无进展生存期（PFS）之间的相关性。采用逻辑回归评估地塞米松剂量与免疫相关不良事件（irAE）发生的相关性。采用单因素和多因素 Cox 比例风险回归模型分析不同地塞米松剂量组之间的生存差异。
预防性地塞米松的剂量与 PFS 无显著相关性（Spearman's rho= -0.103，P=0.098）。单因素[风险比（HR），1.00；P=0.997；HR，0.85；P=0.438]和多因素（HR，0.71；P=0.174；HR，0.87；P=0.512）分析结果均显示，地塞米松与 PFS 之间无显著关联。地塞米松对客观缓解率、疾病控制率或总生存期无显著影响。三组的 irAE 毒性谱相似。
本研究结果表明，在接受 PD-1 阻断治疗和化疗的非鳞状 NSCLC 患者中，预防性使用地塞米松不会对临床结局产生不利影响。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 CAAEs。
