Checkpoint inhibitors in patients with metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

Abstract

BACKGROUND:To the authors' knowledge, outcomes and prognostic tools have yet to be clearly defined in patients with metastatic renal cell carcinoma (mRCC) who are treated with immuno-oncology (IO) checkpoint inhibitors (programmed death-ligand 1 [PD-L1] inhibitors). In the current study, the authors aimed to establish IO efficacy benchmarks in patients with mRCC and update patient outcomes in each International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic class. METHODS: A retrospective analysis was performed using the IMDC database with data from 38 centers. It included patients with mRCC who were treated with ≥1 line of IO. Overall response rates (ORRs), duration of treatment (DOT), and overall survival (OS) were calculated. Patients were stratified using IMDC prognostic factors. RESULTS: A total of 687 patients (90% with clear cell and 10% with non-clear cell) were included. The ORR was 27% in evaluable patients (461 patients). In patients treated with first-line nivolumab and ipilimumab (49 patients), the combination of PD-L1 inhibitor and vascular endothelial growth factor inhibitor (72 patients), and PD-L1 inhibitor (51 patients), the ORR was 31%, 39%, and 40%, respectively, and the median DOT was 8.3 months, 14.7 months, and 8.3 months, respectively. The ORR for second-line, third-line, and fourth-line nivolumab was 22%, 24%, and 26%, respectively. The median DOT was 5.7 months, 6.2 months, and 8.3 months, respectively, in the second-line, third-line, and fourth-line settings. When segregated into IMDC favorable-risk, intermediate-risk, and poor-risk groups, the median OS rates for the first-line, second-line, third-line, and fourth-line treatment settings were not reached (NR), NR, and NR, respectively (P = .163); NR, 26.7 months, and 7.4 months, respectively (P < 0. 0001); 36.1 months, 28.2 months, and 11.1 months, respectively (P = .016); and NR, NR, and 6.7 months, respectively (P = .047). CONCLUSIONS: The ORR was not found to deteriorate from the first-line to the fourth-line of IO therapy. In the second line through fourth line, the IMDC criteria appropriately stratified patients into favorable-risk, intermediate-risk, and poor-risk groups for OS. Cancer 2018;124:3677-3683.

A multicenter retrospective study of nivolumab monotherapy in previously treated metastatic renal cell carcinoma patients: interim analysis of Japanese real-world data

“…In addition to insufficient clinical trial data, there is little real-world evidence in Japanese patients. While there are several reports from other countries [ 13 – 16 ] and some analyses of patient groups excluded from CheckMate 025 [ 17 ], no similar multicenter or large-scale analyses have been reported in Japan. This clinical study was planned to analyze the treatment patterns of nivolumab for mRCC patients in clinical practice, and the efficacy and safety of nivolumab for these patients, by retrospective analyses of information from medical records.…”

Comparative Efficacy of First-Line Immune-Based Combination Therapies in Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-Analysis

“…In addition, we still lack predictive biomarkers and prognostic characteristics in patients or the disease to guide treatment allocation. Results of these phase 3 trials should be interpreted in the context of the International Metastatic RCC Database Consortium (IMDC) risk classification, which has proven its utility since the targeted therapy era [ 12 , 13 ].…”

Rare patients in routine care: Treatment and outcome in advanced papillary renal cell carcinoma in the prospective German clinical RCC‐Registry

“…Since the data cutoff for this analysis was May 15, 2017, more recently approved drugs for mRCC treatment had been documented for only a few (such as for nivolumab) or for none of the patients with pmRCC (such as for cabozantinib). Recent retrospective data suggest that CPI and cabozantinib might be interesting treatment strategies in nccRCC. Further prospective data are warranted, and some clinical trials are ongoing in this field .…”