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
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