Circulating Biomarkers in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma Treated With Everolimus in the Pre-nephrectomy Setting

L Mauge; L Phan; N Benhamouda; I Galy-Fauroux; C Badoual; D Topart; A Thiery-Vuillemin; S Le Moulec; A Guillot; A Cessot; A Mejean; L Albiges; E Tartour; L Fournier; D Helley; S Oudard

doi:10.1016/j.clon.2022.11.012

Circulating Biomarkers in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma Treated With Everolimus in the Pre-nephrectomy Setting

Clin Oncol (R Coll Radiol). 2023 Mar;35(3):e245-e255. doi: 10.1016/j.clon.2022.11.012. Epub 2022 Dec 14.

Authors

L Mauge¹, L Phan², N Benhamouda³, I Galy-Fauroux⁴, C Badoual⁵, D Topart⁶, A Thiery-Vuillemin⁷, S Le Moulec⁸, A Guillot⁹, A Cessot¹⁰, A Mejean¹¹, L Albiges¹², E Tartour³, L Fournier¹³, D Helley¹, S Oudard¹⁴

Affiliations

¹ Université Paris Cité, Inserm, PARCC, F-75015 Paris France; Service d'Hématologie biologique, AP-HP, Hôpital européen Georges-Pompidou, F-75015 Paris, France.
² Association Pour la Recherche de Thérapeutiques Innovantes en Cancérologie, Paris, France.
³ Université de Paris Cité, AP-HP, Hôpital Européen Georges Pompidou, Department of Immunotherapy, PARCC UMRS 970, INSERM, Paris, France.
⁴ Université Paris Cité, Inserm, PARCC, F-75015 Paris France.
⁵ Université Paris Cité, Inserm, PARCC, F-75015 Paris France; Service d'Anatomopathologie, AP-HP, Hôpital européen Georges-Pompidou, F-75015 Paris, France.
⁶ Montpellier University Hospital, Hôpital Saint Eloi, Department of Medical Oncology, Montpellier, France.
⁷ Centre Hospitalier Régional Universitaire CHRU Minjoz, Department of Medical Oncology, Besançon, France.
⁸ Université Paris Cité, Inserm, PARCC, F-75015 Paris France; Service d'Immunologie biologique, AP-HP, Hôpital européen Georges-Pompidou, F-75015 Paris, France.
⁹ Institut Cancérologie Lucien Neuwirth, Department of Medical Oncology, Saint Priest en Jarez, France.
¹⁰ Institut Henri Hartmann, Department of Medical Oncology, Neuilly sur Seine, France.
¹¹ Université Paris Cité, F-75015 Paris France; Service d'Urologie biologique, AP-HP, Hôpital européen Georges-Pompidou, F-75015 Paris, France.
¹² Institut Gustave Roussy, Department of Medical Oncology, INSERM U753, Villejuif, France.
¹³ Université Paris Cité, Inserm, PARCC, F-75015 Paris France; Service de Radiologie, AP-HP, Hôpital européen Georges-Pompidou, F-75015 Paris, France.
¹⁴ Université Paris Cité, Inserm, PARCC, F-75015 Paris France; Service d'Oncologie médicale, AP-HP, Hôpital européen Georges-Pompidou, F-75015 Paris, France. Electronic address: [email protected].

PMID: 36526521
DOI: 10.1016/j.clon.2022.11.012

Abstract

Many drugs are available in renal cell carcinoma (RCC), yet clinicians are still looking for predictive biomarkers of disease recurrence or progression supporting more personalised treatments. An assessment of circulating biomarkers over time was carried out in this French, open-label, single-arm, multicentre trial conducted in 25 patients with either locally advanced (n = 14) or metastatic RCC (n = 11) who received everolimus (10 mg daily) for 6 weeks prior to nephrectomy (NEORAD, NCT01715935). Circulating biomarkers, including circulating tumour cells, haematopoietic and endothelial cells, plasma angiogenesis and inflammatory markers were quantified at baseline, upon everolimus and post-nephrectomy. We assessed tumour burden, objective response rate upon RECIST1.1, disease-free survival (DFS) and progression-free survival (PFS). The correlation between circulating biomarkers was evaluated with multiple factor analysis and biomarker association with DFS/PFS by Cox regression. No objective response rate was obtained before nephrectomy. Upon everolimus, neutrophils, platelets and sVEGFR2 significantly decreased. We did not find any association between circulating biomarkers and DFS/PFS, but patients with the highest tumour burden at baseline had significantly higher plasma levels of interleukin-6, an inflammatory circulating biomarker, and lower levels of sVEGFR2, related to angiogenesis. Further understanding of the link between these circulating biomarkers could help to optimise drug combinations in RCC.

Keywords: Circulating biomarkers; IL-6; everolimus; renal cell cancer; soluble VEGFR2.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents* / therapeutic use
Biomarkers
Carcinoma, Renal Cell* / drug therapy
Carcinoma, Renal Cell* / surgery
Endothelial Cells / pathology
Everolimus / therapeutic use
Humans
Kidney Neoplasms* / drug therapy
Kidney Neoplasms* / surgery
Nephrectomy

Substances

Everolimus
Antineoplastic Agents
Biomarkers