Immune checkpoint inhibitors are standard of care in metastatic renal cell carcinoma but their activity and safety in elderly patients is insufficiently explored. We evaluated outcomes of elderly patients with mRCC treated with nivolumab in the GETUG-AFU 26 NIVOREN phase 2 trial (NCT03013335) and conducted exploratory circulating biomarker analyses.
Patients with mRCC were treated with nivolumab after at least one antiangiogenic therapy. The main endpoint of this analysis was safety in patients ≥ 70 years old (y.o), as per the rate of treatment-related grade 3-5 events (TRAE). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival. Exploration of candidate biomarkers associated with aging included baseline circulating cytokines involved in inflammation, adhesion, immune checkpoints, angiogenesis (IL6, IL7, IL8, BAFF, CXCL13, VCAM-1, 4-1BB, VEGF).
Of 720 patients, 515 were < 70 y.o and 205 ≥ 70 y.o. Patients ≥ 70 y.o exhibited numerically less IMDC poor risk disease (21.0% vs 26.9%), sarcomatoid component (4.9% vs 9.8%) or brain metastases (5.9% vs. 14.7%), but more previous treatment lines (≥ 2 in 54.1% vs 48.5%). TRAE were higher in patients ≥ 70 y.o (24.9% vs. 17.9%, p = 0.033). Respective ORR (19.2% vs. 22.1%) and median PFS (4.5 versus 3.0 months, HR 0.97 [95%CI 0.81-1.15]) were similar. Overall survival was shorter in patients ≥ 70 y.o (19.3 versus 26.9 months, HR 1.26 [95%CI 1.04-1.51]), but not significantly in a competitive risk model. Only V-CAM1 and 4-1BB were found to be increased in patients ≥ 70 y.o.
Nivolumab displayed higher grade 3/4 TRAE but manageable toxicity in elderly patients, with sustained activity. Elderly patients did not display specific inflammatory or angiogenic circulating profiles.
European journal of cancer (Oxford, England : 1990). 2024 Feb 03 [Epub ahead of print]
Loïc Mourey, Larissa Tames Rainho, Cécile Dalban, Lucía Carril-Ajuria, Sylvie Negrier, Christine Chevreau, Gwenaëlle Gravis, Constance Thibault, Brigitte Laguerre, Philippe Barthelemy, Delphine Borchiellini, Marine Gross-Goupil, Lionnel Geoffrois, Frederic Rolland, Antoine Thiery-Vuillemin, Florence Tantot, Nathalie Chaput, Marie Naigeon, Marcus Teixeira, Bernard Escudier, Ronan Flippot, Laurence Albiges
IUCT-Oncopole Claudius Regaud, Toulouse, France., Department of Cancer Medicine, Gustave Roussy, Paris Saclay University, Villejuif, France., Leon Berard Center, University Lyon I, Lyon, France., Institut Paoli-Calmettes, Department of Medical Oncology, Aix Marseille Univ, INSERM, CNRS, CRCM, Immunity and Cancer Team, Marseille, France., Hopital Européen Georges Pompidou, Paris, France., Centre Eugène Marquis, Rennes, France., Institut de Cancérologie Strasbourg Europe, Strasbourg, France., Centre Antoine Lacassagne, Université Côte d'Azur, Nice, France., Department of Medical Oncology, Centre Hospitalier Universitaire Saint-André, Bordeaux, France., Institut de Cancérologie de Lorraine, Vandoeuvre-Lès-Nancy, France., Institut de Cancérologie de l'Ouest, Nantes, France., University Hospital Jean Minjoz, Besançon, France., UNICANCER, Kremlin Bicetre, France., Immunomonitoring Laboratory, UMS CNRS3655 & INSERM US23, Gustave Roussy, Paris Saclay University, Villejuif, France., Department of Cancer Medicine, Gustave Roussy, Paris Saclay University, Villejuif, France; Immunomonitoring Laboratory, UMS CNRS3655 & INSERM US23, Gustave Roussy, Paris Saclay University, Villejuif, France., Department of Cancer Medicine, Gustave Roussy, Paris Saclay University, Villejuif, France; Immunomonitoring Laboratory, UMS CNRS3655 & INSERM US23, Gustave Roussy, Paris Saclay University, Villejuif, France. Electronic address: .