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

Abstract

Abstract Background Baseline corticosteroids exposure was reportedly 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 long-acting, potent corticosteroid that is regularly used in the prevention of chemotherapy-associated adverse events (CAAEs). Given that dexamethasone has potential immunosuppressive properties, it is important to consider its effects on the efficacy of immunotherapy plus chemotherapy in patients with non-squamous NSCLC.Methods 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—Sun Yat-Sen University Cancer Center (SYSUCC), Tongji Hospital of Tongji Medical College (TJH) and Sir Run Run Shaw Hospital of Zhejiang University (SRRSH). The average dosage of prophylactic dexamethasone per chemotherapy cycle was calculated. Patients were divided into three groups based on the dosage 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) time. Univariate and multivariate Cox proportional hazards regression model were used to analyze the differences in PFS among the different groups of dexamethasone dosages.Result The dosage of prophylactic dexamethasone was not significantly correlated with PFS time (Spearman’s rho = -0.103, P = 0.098). The 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 also was not significantly linked to the objective response rate or disease control rate.Conclusion The results of this study suggest that the use of prophylactic dexamethasone did 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.