Author:
Wang Haowei,Liu Fangfang,Chen Xiaoxia,Zhao Chao,Li Xuefei,Zhou Caicun,Hu Jie,Chu Qian,Jiang Tao
Abstract
Abstract
Introduction
Without the clear immunophenotyping of brain metastases (BrMs), the optimal treatment strategy based on PD-1/PD-L1 inhibitor for patients with non-small-cell lung cancer (NSCLC) and BrMs remains unknown.
Methods
308 patients with NSCLC received PD-1/PD-L1 inhibitor-based monotherapy or combination therapy were retrospectively identified. Kaplan-Meier curves with log-rank tests were used to determine the treatment outcomes differences. Transcriptomic analysis of paired primary lung lesions and BrMs were performed to dissect the specific tumor immune microenvironment (TIME) of BrMs.
Results
The presence of BrMs was associated with significantly inferior PFS (2.5 vs. 3.7 months; P = 0.0053) and OS (8.3 vs. 15.4 months; P = 0.0122) in monotherapy group, while it was only associated with poorer PFS (4.6 vs. 7.0 months; P = 0.0009) but similar OS (22.8 vs. 21.0 months; P = 0.9808) in combination treatment group. Of patients with BrMs, PD-1/PD-L1 inhibitor plus antiangiogenic therapy was associated with longest PFS (7.7 vs. 3.2 vs. 2.5 months; P = 0.0251) and OS (29.2 vs. 15.8 vs. 8.3 months; P = 0.0001) when compared with PD-1/PD-L1 inhibitor plus chemotherapy or anti-PD-1/PD-L1 monotherapy. Multivariate analyses suggested that combination treatment was independently correlated with significantly longer PFS (P = 0.028) and OS (P < 0.001) in patients with BrMs. Transcriptomic analysis showed a suppressive TIME in BrMs with decreased CD4+ T cells and M1 macrophages but increased M2 macrophages infiltration.
Conclusion
NSCLC with BrMs obtained barely satisfactory overall benefit from anti-PD-1/PD-L1 monotherapy, partly due to its immunosuppressive TIME. PD-1/PD-L1 inhibitor-based combination treatment, especially anti-PD-1/PD-L1 plus anti-angiogenic treatment, could significantly improve the clinical outcomes of patients with NSCLC and BrMs.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Hematology
Cited by
1 articles.
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