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

San Francisco, CA (UroToday.com) 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:

UroToday_ASCOGU2019-NIVOREN GETUG AFU 26.png

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

References:
  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.
email news signup