Checkpoint inhibitors in patients with metastatic renal cell carcinoma: Results from the international metastatic renal cell carcinoma database consortium

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.

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.

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).

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 Oct 11 [Epub ahead of print]

Steven M Yip, Connor Wells, Raphael Moreira, Alex Wong, Sandy Srinivas, Benoit Beuselinck, Camillo Porta, Hao-Wen Sim, D Scott Ernst, Brian I Rini, Takeshi Yuasa, Naveen S Basappa, Ravindran Kanesvaran, Lori A Wood, Christina Canil, Anil Kapoor, Simon Y F Fu, Toni K Choueiri, Daniel Y C Heng

Department of Medical Oncology, Tom Baker Cancer Center, Calgary, Alberta, Canada., Department of Oncology, Américas Medical Service/Brazil, United Health Group, Sao Paulo, Brazil., Department of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada., Department of Medical Oncology, Stanford University, Stanford, California., Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium., Department of Medical Oncology, IRCCS San Matteo University Hospital Foundation, Pavia, Italy., Department of Medical Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada., Department of Medical Oncology, London Health Sciences Centre, London, Ontario, Canada., Department of Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio., Department of Urology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan., Department of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore., Division of Medical Oncology, QEII Health Sciences Centre, Halifax, Nova Scotia, Canada., Division of Medical Oncology, University of Ottawa, Ottawa, Ontario, Canada., Division of Urology, Juravinski Cancer Centre, McMaster University, Hamilton, Ontario, Canada., Department of Medicine, Auckland City Hospital, Auckland, New Zealand., Department of Medical Oncology, Dana-Farber Cancer Center, Boston, Massachusetts.