2024 World Conference on Lung Cancer (WCLC) - Posters-P4.11E.09 The Efficacy of PD-1/PD-L1 Inhibitors Combined with Chemotherapy and Anti-Angiogenesis Therapy in Driver Gene-Negative NSCLC Brain Metastases

P4.11E.09 The Efficacy of PD-1/PD-L1 Inhibitors Combined with Chemotherapy and Anti-Angiogenesis Therapy in Driver Gene-Negative NSCLC Brain Metastases

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This study investigates the efficacy and mechanisms of combining PD-1/PD-L1 inhibitors with chemotherapy and anti-angiogenesis therapy for treating brain metastases in patients with driver gene-negative lung adenocarcinoma. It includes 179 patients who received various immunotherapy regimens. The research compares four groups: PD-1/PD-L1 inhibitor plus chemotherapy and anti-angiogenesis therapy, PD-1/PD-L1 inhibitor plus chemotherapy, anti-angiogenesis therapy alone, and PD-1/PD-L1 inhibitor monotherapy. Results demonstrated that the combination of PD-1/PD-L1 inhibitors with chemotherapy and anti-angiogenesis therapy achieved the highest median overall survival (21.20 months) and intracranial progression-free survival (15.20 months).<br /><br />The study utilized clinical data from patients treated between May 2020 and July 2022, analyzed through statistical methods such as log-rank tests and Kaplan-Meier survival analysis. To further explore mechanisms, the research used a single-cell RNA sequencing dataset to study LUAD tissues and brain metastases, validating findings at cellular and animal model levels. The research demonstrated that combination therapy activates the immune microenvironment and normalizes vasculature, shown in brain metastasis animal models where this therapy achieved lower tumor fluorescence intensity.<br /><br />Overall, the study concludes that PD-1/PD-L1 blockade, when combined with chemotherapy and anti-angiogenesis therapy, optimizes treatment for this patient group by improving tumor hypoxia, blood-brain barrier permeability, and immune response. This combination decreases M2-type macrophages, increases M1-type macrophages, elevates PD-L1 expression, and boosts CD8 T cells. Additionally, it reduces Rac2 lactylation, inhibits certain chemokine expressions, and promotes TNFSF13 secretion, suggesting promising intervention points for addressing driver gene-negative lung adenocarcinoma brain metastases. This research was funded by grants from the National Natural Science Foundation of China and the Natural Science Foundation of Jiangxi Province.

Asset Subtitle

Anwen Liu

Meta Tag

Speaker Anwen Liu

Topic Metastatic NSCLC – Immunotherapy

Keywords

PD-1/PD-L1 inhibitors

chemotherapy

anti-angiogenesis therapy

brain metastases

lung adenocarcinoma

immunotherapy

single-cell RNA sequencing

immune microenvironment

blood-brain barrier

macrophages