ESMO Virtual Congress 2020: Primary Tumor Response in Patients Treated with Nivolumab for Metastatic Renal Cell Carcinoma - Results of the GETUG-AFU 26 NIVOREN Trial

(UroToday.com) Upfront cytoreductive nephrectomy is no longer recommended in patients treated with tyrosine kinase inhibitors since the CARMENA trial.¹ Response of the primary tumor in mRCC has been described in the TKI era but remains unknown with immune checkpoint inhibitors. At the ESMO 2020 virtual annual meeting, Dr. Jean Courcier and colleagues presented results of their study describing the response of the primary tumor in patients who did not undergo cytoreductive nephrectomy and received nivolumab within the GETUG-AFU-26 NIVOREN study.

Patients who did not undergo cytoreductive nephrectomy in the GETUG-AFU 26 NIVOREN trial, and for whom the primary tumor was evaluated as a target lesion, were included in this analysis:

Patients received nivolumab after the failure of one or more previous treatments, and radiological evaluation was performed every 8-12 weeks (RECIST v1.1). Response rate (ORR), progression-free survival (PFS), and overall survival (OS) were prospectively assessed. Best response in primary tumor size from baseline was considered as a partial response (shrinkage > 30%), stable disease (between -30% and +20%) and progressive disease (growth >20%).

Among 720 patients treated with nivolumab in the NIVOREN GETUG-AFU -26 study, 111 did not undergo cytoreductive nephrectomy, including 67 patients evaluable for response on their primary tumor. This population was predominantly male (76.1%), with a median age of 64 years (min: 33, max: 82), and included 47% poor-risk by IMDC criteria. IMDC risk was favorable in 1.5% of patients and intermediate-risk in 51.5%. Nivolumab was used in 2^nd line for 62% of patients and 3^rd line or more in 38%. With a median follow-up of 26.9 months (95% CI 22.3-28.5), the ORR was 6.0% (4/67) patients), median PFS was 2.8 months (95% CI 2.6-4.2), and OS 16.6 months:

The median size of the primary renal tumor at nivolumab start was 80mm and consisted of>50% of the measured tumor burden (median sum of target lesion diameters 147mm). The median best change in primary tumor size was 5% (range: -51% to +68%). Four patients experienced primary tumor partial response (6.0%), 11 primary tumor progressive disease (16.4%), and 52 primary tumor stabile disease (77.6%). A comparison between the response of the primary and other lesions showed a linear correlation at first, which became uncertain with successive evaluations.

Dr. Courcier concluded his presentation with the following take-home messages:

Patients who did not undergo cytoreductive nephrectomy had adverse baseline characteristics but most achieved primary tumor stabile disease or partial response, as well as prolonged primary tumor control with nivolumab
Study of exceptional responders may provide insights on subsets of patients who may benefit from delayed cytoreductive nephrectomy

Presented by: Jean Courcier, Urology, Hôpital Henri Mondor, APHP, Haute-Garonne, France

Co-Authors: C. Dalban,² B. Laguerre,³ S. Ladoire,⁴ P. Barthélémy,⁵ S. Oudard,⁶ F. Joly,⁷ G. Gravis Mescam,⁸ C.M. Chevreau,⁹ L. Geoffrois,¹⁰ E. Deluche,¹¹ F. Rolland,¹² D. Topart,¹³ S. Culine,¹⁴ S. Négrier,¹⁵ H. Mahammedi,¹⁶ F. Tantot,¹⁷ B. Escudier,¹⁸ R. Flippot,¹⁹ L. Albiges²⁰

Affiliations: 2 Clinical Research Department, Centre Léon Bérard, Lyon, France, 3 Medical Oncology Department, Centre Eugene - Marquis, Rennes, France, 4 Oncology, Centre Georges-François Leclerc (Dijon), Dijon, France, 5 Department of Medical Oncology, Les Hôpitaux Universitaires de Strasbourg/ Institut de Cancérologie Strasbourg Europe, Strasbourg, France, 6 Medical Oncology, Hopital Européen Georges Pompidou, AP-HP.Centre – Université de Paris, Paris, France, 7 Medical Oncology Department, Centre François Baclesse, Caen, France, 8 Medical Oncology Department, Institute Paoli Calmettes, Marseille, France, 9 IUCT-Oncopôle Institut Claudius Regaud, Toulouse, HauteGaronne, France, 10 Medical Oncology, Institut de Cancérologie de Lorraine - Alexis Vautrin, Vandoeuvre Les Nancy, France, 11 Medical Oncology Department, CHU Limoges - Hopital Dupuytren, Limoges, France, 12 Medical Oncology Department, ICO Institut de Cancerologie de l'Ouest René Gauducheau, Saint-Herblain, France, 13 CHU Montpellier, CHU Montpellier, Montpellier, France, 14 Medical Oncology, Hôpital Saint-Louis, Paris, France, 15 Oncologie Urologique, Centre Léon Bérard, Lyon, France, 16 Oncology, Centre Jean Perrin, Clermont Ferrand, Clermont-Ferrand, France, 17 Research & Development Department, Unicancer, Le Kremlin Bicêtre, France, 18 Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France, 19 Medical Oncology, Institut Gustave Roussy, Villejuif, France 20 Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France

Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2020 European Society for Medical Oncology Virtual Congress (#ESMO20), September 19^th-September 21^st, 2020.

References:

Mejean A, Ravaud A, Thezenas S, et al. Sunitinib alone or after nephrectomy in metastatic renal cell carcinoma. N Engl J Med 2018 Aug 2;379(5):417-427.

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