VEGF-A blockade overcomes liver metastases resistance to chemoimmunotherapy in patients with advanced non-squamous NSCLC

作者：Matthieu Roulleaux Dugage, Andrey Yurchenko, Sergey Nikolaev, Barzin Y. Nabet, Stéphanie Corgnac, C. Anquetil, Minu K. Srivastava, Velimir Gayevskiy, Virginia Mcnally, Laura Mezquita, Jean‐Luc Perfettini, Séverine Mouraud, Christophe Massard, Benjamin Besse, Yohann Loriot, Aurélien Marabelle, Nathalie Chaput, Édouard Auclin · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2026 · DOI：10.1136/jitc-2026-014991 · 被引用次数：1 · 研究领域：Cancer Immunotherapy and Biomarkers、Angiogenesis and VEGF in Cancer、Hepatocellular Carcinoma Treatment and Prognosis

PURPOSE: Liver metastases (LMs) confer resistance to immune checkpoint blockade in advanced non-squamous non-small cell lung cancer (ns-NSCLC), likely through an immunosuppressive tumor microenvironment (TME). We hypothesized that vascular endothelial growth factor (VEGF)-A blockade, by remodeling the immunosuppressive TME, could restore the benefit of chemoimmunotherapy in LM+ patients. Here, we report the first comparative analysis of chemoimmunotherapy with and without bevacizumab specifically in this population. EXPERIMENTAL DESIGN: Data were analyzed from the phase III IMpower130 and IMpower150 trials in treatment-naïve, EGFR/ALK-wild-type patients with ns-NSCLC. Treatment arms included chemotherapy (CT), CT plus atezolizumab (CT+immunotherapy (IT)), CT plus bevacizumab (CT+antiangiogenic (AA)), and CT+IT+ AA, with LM as a stratification factor. Survival outcomes were assessed by Kaplan-Meier estimates and multivariate Cox regression analyses. Bulk and single-cell RNA sequencing data were used to characterize the LM TME. RESULTS: Among 1,713 patients, 236 (13.8%) presented with LMs. In IMpower130, LM+ patients derived no overall survival (OS) benefit from CT plus IT (CT+IT) compared with CT alone (HR for OS: 1.05; 95% CI 0.63 to 1.73). In contrast, in IMpower150, the addition of bevacizumab to CT+IT (CT+IT+ AA) significantly improved progression-free survival (PFS; HR: 0.49) and OS (HR: 0.52) in LM+ patients-an effect not observed in patients without LM. Baseline transcr...