Vasculo-immune modulatory effects of anti-VEGF therapy in metastatic clear cell renal cell carcinoma: The A-PREDICT trial.

作者：Lewis Au, Zayd Tippu, Husayn Ahmed Pallikonda, Anne-Laure Cattin, Georgia Whitton, Andrew Rowan, Annika Fendler, Jahangeer Malik, Ekaterini Boleti, Naveen Vasudev, Martin Highley, Agnieszka Michael, Tim Eisen, Steven Penegar, Rebecca Lewis, Lucy Kilburn, Judith M. Bliss, Charles Swanton, James Larkin, Samra Turajlic · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.5_suppl.572 · 被引用次数：2 · 研究领域：Renal cell carcinoma treatment、Renal and related cancers

572 Background: Anti-vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors and checkpoint inhibitors (CPI) a standard-of-care treatment for clear cell renal cell carcinoma (ccRCC). We investigated the biology underpinning benefit of anti-VEGFR TKI in the phase II A-PREDICT trial (NCT01693822), evaluating pre- and post-treatment, fresh multiregion tumour biopsies in patients with metastatic ccRCC treated with first-line axitinib. Methods: We analysed 123 tumour samples from 52 patients, 28 with paired pre/post-treatment samples. Post-treatment samples included week-9, nephrectomy, and on-progression timepoints. ‘Responders’ had progression-free survival (PFS) ≥6 months (n=35), ‘non-responders’ with PFS <6 months (n=17). We applied a custom Nanostring panel for gene expression analysis and multiplex immunofluorescence (mIF) for orthogonal validation. Wilcoxin test was used to analyze paired observations. Results: At baseline, angiogenesis scores were similar between responders and non-responders (p=0.22). Post-treatment, the angiogenesis, vascular sprouting, and endothelial cell proliferation signature scores were significantly decreased (p=0.023, 0.0034, & 0.0082, respectively) in all patients, suggesting suppression of angiogenesis and neovascularisation irrespective of clinical outcomes. mIF in 3 patients (with PFS of 3, 5.6, & 100 months) confirms widespread intratumoral vessel depletion. Immune deconvolution analysis shows total levels of T cells ...