Department of Oncology, the Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Institute of Intestinal Diseases, Tongji University School of Medicine, Shanghai, China.
Int Immunopharmacol. 2021 Oct;99:108031. doi: 10.1016/j.intimp.2021.108031. Epub 2021 Aug 3.
Immunotherapies targeting immune checkpoints have achieved encouraging survival benefits in patients with various solid cancers. Corticosteroids are frequently administrated for cancer/non-cancer related indications and immune-related adverse events (irAEs). This study aimed to clarify the prognostic significance of corticosteroid administration in solid cancer patients receiving immune checkpoint inhibitor (ICI) treatment.
First, a meta-analysis was performed using the literatures searched from PubMed, Cochrane Library, Web of Science, Embase, and Clinicaltrials.gov before January 2021. The Hazard ratios (HRs) coupled with 95% confidence intervals (CIs) were used to evaluate the correlation of corticosteroid administration with overall survival (OS) and progression-free survival (PFS). Then, a retrospective analysis enrolling 118 ICI-treated cancer patients was performed for validation, among which 26 patients received corticosteroids for cancer-related indications.
In the meta-analysis, corticosteroid administration for cancer-related indications was significantly correlated with worse PFS (HR = 1.735(1.381-2.180)) and OS (HR = 1.936(1.587-2.361)) of the ICI-treated patients. However, corticosteroid administration for non-cancer-related indications and irAEs was unrelated with PFS (non-cancer-related indications: HR = 0.830(0.645-1.067); irAEs: HR = 1.302(0.628-2.696)) and OS (non-cancer-related indications: HR = 0.786(0.512-1.206); irAEs: HR = 1.107(0.832-1.474)) of the ICI-treated patients. The following retrospective analysis identified corticosteroid administration for cancer-related indications was an independent unfavorable predictor for PFS (P = 0.006) and OS (P = 0.044) of the ICI-treated patients. The subgroup analysis based on non-small cell lung cancer (NSCLC) demonstrated the similar results (P = 0.002 for PFS and P = 0.047 for OS).
Our study demonstrated corticosteroid administration for cancer-related indications is an unfavorable prognostic factor in solid cancer patients receiving ICI treatment. Therefore, careful selection of corticosteroid-treated patients for ICI therapy is quite necessary in individualized clinical management.
针对免疫检查点的免疫疗法在各种实体瘤患者中取得了令人鼓舞的生存获益。皮质类固醇经常用于癌症/非癌症相关的适应证和免疫相关不良事件(irAE)。本研究旨在阐明在接受免疫检查点抑制剂(ICI)治疗的实体瘤患者中皮质类固醇给药的预后意义。
首先,对 2021 年 1 月前从 PubMed、Cochrane Library、Web of Science、Embase 和 Clinicaltrials.gov 检索到的文献进行了荟萃分析。使用风险比(HR)和 95%置信区间(CI)来评估皮质类固醇给药与总生存期(OS)和无进展生存期(PFS)的相关性。然后,对 118 名接受 ICI 治疗的癌症患者进行了回顾性分析以验证,其中 26 名患者因癌症相关适应证接受皮质类固醇治疗。
荟萃分析显示,癌症相关适应证的皮质类固醇给药与 ICI 治疗患者的 PFS(HR=1.735(1.381-2.180))和 OS(HR=1.936(1.587-2.361))更差显著相关。然而,非癌症相关适应证和 irAE 皮质类固醇给药与 PFS(非癌症相关适应证:HR=0.830(0.645-1.067);irAE:HR=1.302(0.628-2.696))和 OS(非癌症相关适应证:HR=0.786(0.512-1.206);irAE:HR=1.107(0.832-1.474))无关。以下回顾性分析确定癌症相关适应证的皮质类固醇给药是 ICI 治疗患者 PFS(P=0.006)和 OS(P=0.044)的独立不良预后因素。基于非小细胞肺癌(NSCLC)的亚组分析显示了相似的结果(PFS 为 0.002,OS 为 0.047)。
我们的研究表明,癌症相关适应证的皮质类固醇给药是接受 ICI 治疗的实体瘤患者的不利预后因素。因此,在个体化临床管理中,对于接受 ICI 治疗的皮质类固醇治疗患者进行仔细选择非常必要。