Nivolumab in Metastatic Clear-cell Renal Cell Carcinoma: An Integrative Biomarker Analysis from the NIVOREN GETUG-AFU 26 Phase 2 Study.

Fiche publication

Date publication

novembre 2025

Journal

European urology

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BARTHELEMY Philippe , Dr GEOFFROIS Lionnel , Dr LADOIRE Sylvain , Dr THIERY-VUILLEMIN Antoine

Tous les auteurs :
Flippot R, Vano YA, Dalban C, Beuselinck B, Fléchon A, Meylan M, Pouessel D, Bougoüin A, Sautes-Fridman C, Gravis G, Chaput N, Oudard S, Desnoyer A, Laguerre B, Chouaib S, Barthelemy P, Borchiellini D, Carril-Ajuria L, Gross-Goupil M, Fridman WH, Geoffrois L, Rolland F, Thiery-Vuillemin A, Joly F, Ladoire S, Tantot F, Chabaud S, Escudier B, Rioux-Leclercq N, Albiges L,

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/41224576

Résumé

Nivolumab improved survival in patients with refractory metastatic clear-cell renal cell carcinoma (ccRCC), but no reliable biomarker of activity has been identified. We conducted a real-world phase 2 trial of nivolumab in patients progressing after one or more vascular endothelial growth factor (VEGF) receptor-directed therapies, which included an integrated translational programme. Candidate tissue and circulating biomarkers were assessed using immunoassays and gene expression profiling. Overall, 720 patients were treated, with activity and safety in line with pivotal trial data. Exploration of tissue architecture showed that the presence of tertiary lymphoid structures, CD8+ lymphocytes, and CD163+ macrophage infiltration at the invasive margin were all marginally associated with longer progression-free survival, similarly to PD-1 expression on immune cells. Expression of hypoxia-related marker VEGF on tumour cells was however strongly associated with shorter progression-free and overall survival. Recapitulation of microenvironment composition based on gene expression signatures showed that patients harbouring a high tumour lymphocyte infiltration, concomitantly to low infiltration of neutrophil and non-immune stromal cells, had improved response to nivolumab. Conversely, circulating cytokines related to protumoral inflammation interleukin (IL)-6 and IL-8 were independently associated with shorter progression-free and overall survival. Overall, immune and angiogenic features helped inform outcomes to nivolumab. Circulating factors were best potential predictors for immunotherapy activity in ccRCC.