Safety and efficacy of nivolumab in metastatic renal cell carcinoma (mRCC): Final analysis from the NIVOREN GETUG AFU 26 study.

Abstract

542 Background: NIVOREN GETUG AFU 26 study, is a French multicenter prospective study to evaluate safety and efficacy of Nivolumab (N) in a broad “real world setting” in mRCC after failure of 1 or 2 tyrosine kinase inhibitors. Methods: Between February 2016 and June 2017, 729 pts have been enrolled across 27 institutions. Primary objective of the trial was safety assessed by grade ≥ 3 treatment related adverse event (TRAE). Results: Overall, 720 patients treated with N were included in this final analysis. All pts had clear cell mRCC. Median age was 64 years old, 77.4% were male, 84.7% had prior nephrectomy. ECOG PS was >1 in 15.0%, 21.3% pts had received prior everolimus, 22.4% pts had received more than 2 previous lines, IMDC risk groups were 18.3%/56.2%/25.5% for good/intermediate and poor risk respectively. Brain Metastasis at screening was noted in 83 (12.3%) pts. With a median follow up of 20.9 months (mo), median duration of treatment was 5.2 mo (0.5; 28.1) with 15% of pts still on therapy. Median PFS was 3.2 IC 95% [2.9; 4.6] mo. At the time of this analysis, 316 pts have died and 12 mo OS rate was 69% IC 95% [66; 73]. Objective response rate was 20.8% (1.2% CR, 19.6%PR). Stable disease was seen in 31.6% and PD in 47.6%. Noteworthy, 46.1% of pts were treated beyond progression. Overall, 123 pts (17.1%) have presented at least one grade ≥ 3 TRAE, including asthenia (2.4%), metabolic disorders (2.1%), gastro-intestinal disorders (1 .9%), musculoskeletal (1.7%), renal disorders (1.3%), hematologic (1.3%). 6 patients have developed grade 5 toxicity (2 cardiac failure, 1 macrophage activation syndrom, 1 Cerebral hemorrhage, 1 unknown). Treatment discontinuation due to any grade TRAE occurred in 54 pts (7.5%). Interestingly, pts with grade ≥ 3 TRAE had longer PFS than pts without grade ≥ 3 TRAE (HR 0.69 [0.55-0.87]). Conclusions: We report the primary objective analysis of the largest prospective real world setting study of N in mRCC. NIVOREN study demonstrates that N safety and efficacy in a “real world” prospective study are similar to the pivotal study. Grade ≥ 3 TRAE was associated with longer PFS. Clinical trial information: NCT03013335.