ASCO GU 2019: Final Analysis from the NIVOREN GETUG AFU 26 Study

San Francisco, CA ( The final presentation of GU ASCO 2019 featured Dr. Laurence Albiges presenting results from the final analysis of the NIVOREN GETUG AFU 26 study. This was a French multicenter prospective study to evaluate the safety and efficacy of nivolumab in a broad “real world setting” in mRCC after failure of 1 or 2 tyrosine kinase inhibitors. CheckMate 025 tested nivolumab vs everolimus in the pre-treated mRCC in a landmark phase III clinical trial1. This trial randomized 821 patients 1:1 to receive 3 mg/kg of nivolumab IV every 2 weeks or a 10-mg everolimus tablet orally once daily. The median overall survival (OS) was 25.0 months (95%CI 21.8-NE) with nivolumab and 19.6 months (95%CI 17.6-23.1) with everolimus (HR 0.73, 98.5%CI 0.57-0.93). The objective response rate (ORR) was greater with nivolumab than with everolimus (25% vs. 5%; OR 5.98, 95%CI 3.68-9.72) and median progression-free survival PFS was 4.6 months (95%CI 3.7-5.4) with nivolumab and 4.4 months (95%CI 3.7-5.5) with everolimus (HR 0.88, 95%CI 0.75-1.03). Grade 3 or 4 treatment-related adverse events occurred in 19% of the patients receiving nivolumab and in 37% of the patients receiving everolimus. Given that patients in clinical trials are selected based on stringent inclusion criteria, it is important to assess outcomes in the real-world setting.

NIVOREN GETUG AFU 26 enrolled 720 patients between January 2016 and July 2017 across 26 institutions in France. Inclusion criteria allowed performance status 0-2, >2 prior lines of therapy, prior mTOR inhibitor therapy, asymptomatic brain metastases, and impaired renal function (CrCl >40 mml/min). Patients must have had a component of clear cell histology.  The primary objective of the trial was safety assessed by grade ≥ 3 treatment related adverse event.

he median patient age was 64 years old (range 22-90), 77.2% were male, and 84.6% had a prior nephrectomy. ECOG performance status was >1 in 15.1%, 21.4% patients had received prior everolimus, 22.4% pts had received more than two previous lines of therapy, and IMDC risk group breakdown was 18.3%/56.2%/25.5% for good/intermediate and poor risk, respectively; brain metastasis at screening was noted in 83 (12.3%) patients.

Over a median follow up of 23.9 months, the median duration of treatment was 5.2 months with 15% of patients still on therapy. Regarding the primary outcome of safety, 129 patients (17.9%) had at least one grade ≥ 3 treatment related adverse event, including asthenia (3.5%), metabolic disorders (2.1%), gastrointestinal disorders (2 .2%), musculoskeletal (1.7%), renal disorders (1.4%), hematologic (1.3%). There six treatment related mortalities, including two from cardiac failure, one from macrophage activation syndrome, one from a cerebral hemorrhage, one from pneumonia, and one unknown. Treatment discontinuation due to any grade treatment related adverse event occurred in 64 patients (8.9%), however those with grade ≥ 3 treatment related adverse event had longer PFS than those without grade ≥ 3 treatment related adverse event (HR 0.69, 95%CI 0.56-0.86). Median PFS was 3.2 months (95%CI 2.9-4.6). At the time of this analysis, 316 patients had died and 12-month OS rate was 69% (95%CI 66-73). The median OS for favorable risk patients was 32.8 months (95%CI 28.7-NE), 25.0 months (95%CI 21.5-30.7) for intermediate risk, and 10.4 months (95%CI 7.0-14.5) for poor risk. The ORR was 21.0%, with 1.3% patients experiencing complete response, and 19.7% partial response; stable disease was seen in 31.1% and progressive disease in 47.9%. There were 47.0% of patients treated beyond progression. Among the overall population, 381 received subsequent therapy (59%) and median time to subsequent therapy was 8.1 months (95%CI 7.3-9.0), most commonly cabozantinib (27.5%) and axitinib (12.9%). Several subgroup analyses were performed for PFS:


Dr. Albiges concluded her presentation of NIVOREN GETUG AFU 26 with several take-home messages:
  • This is the largest prospective real world setting study of nivolumab in mRCC
  • Nivolumab safety and efficacy in a “real-world” prospective study is similar to the pivotal clinical trial
  • Grade ≥3 treatment related adverse events occurred in 17.9%, with a median time to the first event of 3.3 months, but was associated with longer PFS
Clinical trial information: NCT03013335

Presented by: Laurence Albiges, MD, PhD, Institut Gustave Roussy, Universite Paris-Sud, Villejuif, France
Co-Authors: Sylvie Negrier, Cécile Dalban, Christine Chevreau, Gwenaelle Gravis, Stephane Oudard, Brigitte Laguerre, Philippe Barthelemy, Delphine Borchiellini, Marine Gross-Goupil, Lionnel Geoffrois, Frederic Rolland, Antoine Thiery-Vuillemin, Florence Joly, Sylvain Ladoire, Florence Tantot, Bernard Escudier, GETUG; Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France, Villejuif, France; Centre Léon Bérard, Lyon, France; IUCT-Oncopôle Institut Claudius Regaud, Toulouse, France; Medical Oncology, Institut Paoli-Calmettes, Marseille, France; Hopital Europeen Georges Pompidou, Paris, France; Centre Eugène Marquis, Rennes, France; Medical Oncology, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; Centre Antoine Lacassagne, Nice, France; Oncology Department, Centre Hospitalier Universitaire Saint-Andre, Bordeaux, Aquitaine, France, Bordeaux, France; Department of Medical Oncology, Institut de Cancérologie de Lorraine, Vandœuvre-Lès-Nancy, France; Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Nantes, France; University Hospital Jean Minjoz, Besançon, France; Centre Francois Baclesse, Caen, France; Department of Medical Oncology, Center GF Leclerc, Dijon Cedex, France; UNICANCER, Kremlin Bicetre, France; U1015 INSERM, Gustave Roussy Cancer Campus, Paris Saclay University, 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 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA

  1. Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 2015;373(19):1803-1813.