ASCO GU 2018: Safety and Efficacy of Nivolumab in Metastatic Renal Cell Carcinoma: Results From the NIVOREN GETUG-AFU 26 Study

San Francisco, CA ( The response rates seen in clinical trials tend to be inferior once translated into the community, mainly due to the under-representation of elderly, highly comorbid and heavily pre-treated patients into clinical trials.  The investigators of the NIVOREN-GETUG AFU 26 study aimed to replicate the CheckMate 025 trial using a “real world” setting. In review, the CheckMate 025 trial compared nivolumab to everolimus in the second/third-line setting, showing a significant improvement in objective response rates (ORR) and overall survival (OS), along with significant improvements in the rate of serious adverse events. 

The NIVOREN GETUG-AFU 26 study, was a multicenter trial including 26 centers across France which aimed to study the safety and efficacy of nivolumab in a “real world” setting. The inclusion criteria for the trial was modified from the one use in CheckMate 025 to better represent a “real world” setting, by allowing the participation of patients with inferior performance status (PS-2), prior treatment with mTOR inhibitor, presence of asymptomatic brain metastases, impaired renal function (CrCl > 40ml/min), and failure of more than 2 prior therapies. The study enrolled 729 patients over an 18-month period. The analysis presented is based on the first 528 patients to ensure a median follow-up of at least 12 months. On review of the baseline characteristics, 15% of patients presented with a diminished performance status (PS-2), 25% with poor-risk IMDC criteria, 50% had received at least 2 or more prior therapies, 14% presented with asymptomatic brain metastases, and 25% had been previously treated with everolimus. Treatment discontinuation occurred in 71% of patients, the majority related to disease progression (50%) with only 10% due to adverse event/toxicity. Grade 3/4 adverse events occurred in a total of 77 pts (14.6%), which was lower than that reported in the landmark trial (CheckMate 025). Only four treatment-related deaths  occurred at the time of interim analysis (2 cardiac failure, 1 macrophage activation, and 1 pneumonitis). 

In regards to treatment effectiveness, an ORR rate was observed in 18.5% of patients, with 2 patients achieving a complete response, and 34.3% stable disease. The median progression-free and overall survival were 4 months [2.9-4.6] and 18.6 months [16-18.6], respectively. On subgroup analysis, patients with poor performance status (HR 2.40 [CI 1.7-3.4], p<0.001) and those previously treated with everolimus (HR 1.39 [1.01-1.92], p=0.044) had a worse overall survival. Interestingly, the presence of asymptomatic brain metastases or renal dysfunction did not result in worse progression-free or overall survival. Compared to CheckMate 025 the NIVOREN GETUG-AFU 26 trial showed comparable results although it represented a sicker and significantly more pretreated population (Table 2). 

In summary, the NIVOREN GETUG-AFU 26 is the largest prospective “real world” setting study of nivolumab in patients with metastatic kidney cancer. The study demonstrated that nivolumab performs well in a real setting population further establishing checkpoint inhibitors as the main agent for treatment of metastatic renal cell carcinoma in the second/third-line setting. 

Presented by: Laurence Albiges, MD, PhD, Institut Gustave Roussy, Villejuif, France

Written by: Andres F. Correa, MD, Fox Chase Cancer Center, Philadelphia, PA at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA