Adrenal Metastases Are Associated with Poor Outcomes in Patients with Metastatic Clear Cell Renal Cell Carcinoma Treated with Nivolumab in the GETUG-AFU-26 NIVOREN Phase 2 Trial

Emilien Billon; Cécile Dalban; Stephane Oudard; Christine Chevreau; Brigitte Laguerre; Philippe Barthélémy; Delphine Borchiellini; Lionnel Geoffrois; Sylvie Negrier; Florence Joly; Antoine Thiery-Vuillemin; Marine Gross-Goupil; Frederic Rolland; Frank Priou; Hakim Mahammedi; Florence Tantot; Bernard Escudier; Sylvie Chabaud; Laurence Albiges; Gwenaelle Gravis

doi:10.1016/j.euo.2023.09.009

Adrenal Metastases Are Associated with Poor Outcomes in Patients with Metastatic Clear Cell Renal Cell Carcinoma Treated with Nivolumab in the GETUG-AFU-26 NIVOREN Phase 2 Trial

Eur Urol Oncol. 2023 Oct 7:S2588-9311(23)00200-6. doi: 10.1016/j.euo.2023.09.009. Online ahead of print.

Authors

Emilien Billon¹, Cécile Dalban², Stephane Oudard³, Christine Chevreau⁴, Brigitte Laguerre⁵, Philippe Barthélémy⁶, Delphine Borchiellini⁷, Lionnel Geoffrois⁸, Sylvie Negrier², Florence Joly⁹, Antoine Thiery-Vuillemin¹⁰, Marine Gross-Goupil¹¹, Frederic Rolland¹², Frank Priou¹³, Hakim Mahammedi¹⁴, Florence Tantot¹⁵, Bernard Escudier¹⁶, Sylvie Chabaud², Laurence Albiges¹⁶, Gwenaelle Gravis¹⁷

Affiliations

¹ Institut Paoli-Calmettes, Aix-Marseille Université, Marseille, France. Electronic address: billone@ipc.unicancer.fr.
² Centre Léon Bérard, Lyon, France.
³ Hôpital Européen Georges-Pompidou, University of Paris, Paris, France.
⁴ IUCT-Oncopôle Institut Claudius Regaud, Toulouse, France.
⁵ Centre Eugéne Marquis, Rennes, France.
⁶ Institut de Cancérologie Strasbourg Europe, Strasbourg, France.
⁷ Centre Antoine Lacassagne, Université Côte d'Azur, Nice, France.
⁸ Institut de Cancérologie de Lorraine, Centre Alexis Vautrin, Vandoeuvre-Lès-Nancy, France.
⁹ Centre François Baclesse, Caen, France.
¹⁰ University Hospital Jean Minjoz, Besançon, France.
¹¹ Centre Hospitalier Universitaire de Bordeaux-Hôpital Saint-André, Bordeaux, France.
¹² Institut de Cancérologie de l'Ouest, Saint-Herblain, France.
¹³ CHD Vendee-Hopital Les Oudairies, La Roche-Sur-Yon, France.
¹⁴ Centre Jean Perrin, Clermont-Ferrand, France.
¹⁵ GETUG Group, UNICANCER, Paris, France.
¹⁶ Gustave Roussy, Villejuif, France.
¹⁷ Institut Paoli-Calmettes, Aix-Marseille Université, Marseille, France.

PMID: 37813745
DOI: 10.1016/j.euo.2023.09.009

Abstract

Background: Glandular metastases (GMs; adrenal gland, pancreas, thyroid, ovary, breast, or prostate) are rare in metastatic clear cell renal cell carcinoma (mccRCC). Previous studies have indicated that GM patients treated with antiangiogenic therapy experience significantly longer overall survival (OS).

Objectives: To assess outcomes for mccRCC with or without GMs treated with nivolumab.

Design, setting, and participants: The GETUG-AFU-26 NIVOREN phase 2 trial evaluated the activity and safety of nivolumab in patients with mccRCC who experienced failure of antiangiogenic therapies (NCT03013335). In this ancillary study, patients were divided into two groups according to the presence or absence of at least one GM.

Outcome measurements and statistical analysis: The primary outcome was OS; secondary outcomes were progression-free survival (PFS) and the objective response rate (ORR). Survival was estimated using the Kaplan-Meier method. Univariate and multivariable Cox regression models are used to estimate the hazard ratio (HR) with 95% confidence interval (CI) for survival outcomes. Subgroup analyses were performed for patients with pancreatic metastases and patients with adrenal metastases.

Results and limitations: Among 720 patients treated with nivolumab between February 2016 and July 2017, 217 had GMs, of whom 151/217 had adrenal metastases and 86/217 had pancreatic metastasis. Patients with adrenal metastases had worse 12-mo OS (64% vs 71.1%) and 6-mo PFS (27.2% vs 36.6%) and a lower objective response rate (12.5%, 95% CI 7.6%-19.0%, vs 23.2%, 95% CI 19.8-27.0%; p = 0.005) than patients without adrenal metastases. Conversely, univariate analysis showed that patients with pancreatic metastases had significantly better 12-mo OS (82.3% vs 67.9%; HR 0.59, 95% CI 0.40-0.85) in comparison to patients with nonpancreatic GMs. On multivariable analysis, only adrenal metastasis remained associated with adverse prognosis.

Conclusions: Adrenal metastasis is an independent prognostic factor for poor response and survival in the GETUG-AFU-26 NIVOREN trial. Limited activity with nivolumab was observed for patients with mccRCC with adrenal metastases. These results warrant an evaluation of the prognostic value of adrenal metastases in patients treated with immunotherapy combinations with ipilimumab or tyrosine kinase inhibitors.

Patient summary: Our study showed that metastasis in the adrenal glands could be an independent factor associated with poor response to immunotherapy and survival for patients with metastatic kidney cancer. It would be useful to evaluate the prognostic value of adrenal gland metastasis in patients treated with immunotherapy combinations or immunotherapy agents combined with drugs called tyrosine kinase inhibitors.

Keywords: Adrenal metastases; GETUG-AFU-26 NIVOREN trial; Glandular metastases; Immunotherapy; Nivolumab; Pancreatic metastases; Renal cell carcinoma.