ASCO GU 2018: Differential Expressions of PD-1, PD-L1, and PD-L2 Between the Primary and Metastatic Sites in Renal Cell Carcinoma

San Francisco, CA ( The immune checkpoint inhibitor nivolumab, an anti PD-1 monoclonal antibody, and the tyrosine kinase inhibitor (TKI) cabozantinib have both been shown in phase III clinical trials to be effective in metastatic renal cell carcinoma (mRCC) after progression on first-line therapy.1,2 The authors, some of whom were involved in the original studies, went on to assess the real-world efficacy of these therapies in second-line mRCC.

Using the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) of 8798 patients from 35 centers, they performed a retrospective analysis on mRCC patients treated with second-line nivolumab or cabozantinib. Baseline characteristics and IMDC risk factors were collected. Overall survival (OS), time to treatment failure (TTF), and response rates were determined for each therapy.

A total of 225 patients were treated with nivolumab and 53 were treated with cabozantinib. Both groups were relatively similar, 80% male, 20% KPS <80, 80-90% had nephrectomy, 16-19% non-clear cell histology, and similar IMDC criteria. Cabozantinib patients were older (29% greater than 70, vs 9% in the nivolumab arm). CR rates and PR rates were similar.

There was no significant difference in OS identified, with a mOS for nivolumab of 22.1 months (95% CI 17.18 – NR) and 23.7 months (95% CI 15.52 vs. NR) for cabozantinib, p = 0.6053. The TTF was also similar, with 6.90 months (95% CI 4.60 – 9.20) for nivolumab versus 7.39 months (95% CI 5.52 – 12.85) for cabozantinib, p = 0.1983. The adjusted hazard ratio (HR) for nivolumab vs. cabozantinib was 1.297 (95% CI – 0.728 – 2.312), p = 0.3775.

Based on this real-world analysis, as there is no head-to-head comparison, nivolumab and cabozantinib appear to have similar efficacy in terms of OS and TTF. Thus both novel agents are reasonable therapeutic options for patients progressing after initial first-line therapy.

Speaker: Igor Stukalin

Co-Authors: J Connor Wells, Jeffrey Graham, Takeshi Yuasa, Benoit Beuselinck, Christian K. Kollmannsberger, D. Scott Ernst, Neeraj Agarwal, Tri Le, Frede Donskov, Aaron Richard Hansen, Georg A. Bjarnason, Sandy Srinivas, Lori Wood, Ajjai Shivaram Alva, Ravindran Kanesvaran, Simon Yuen Fai Fu, Ian D. Davis, Toni K. Choueiri, Daniel Yick Chin Heng

Institution(s): Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada; University of Manitoba, Winnipeg, MB, Canada; Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan; University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium; British Columbia Cancer Agency - Vancouver Centre, Vancouver, BC, Canada; London Health Sciences Centre, London, ON, Canada; Huntsman Cancer Hospital, Salt Lake City, UT; UT Southwestern Medical Center, Dallas, TX; Aarhus University Hospital, Aarhus, Denmark; Princess Margaret Cancer Centre, Toronto, ON, Canada; Sunnybrook Research Institute, Toronto, ON, Canada; Stanford University, Stanford, CA; QEII Health Sciences Centre, Halifax, NS, Canada; University of Michigan, Ann Arbor, MI; National Cancer Centre Singapore, Singapore, Singapore; Auckland City Hospital, Auckland, New Zealand; Monash University Eastern Health Clinical School, Victoria, Australia; Dana-Farber Cancer Institute/ Brigham and Women’s Hospital/ Harvard Medical School, Boston, MA

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA

1. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Choueiri TK, Gurney H, Donskov F, Bono P, Wagstaff J, Gauler TC, Ueda T, Tomita Y, Schutz FA, Kollmannsberger C, Larkin J, Ravaud A, Simon JS, Xu LA, Waxman IM, Sharma P; CheckMate 025 Investigators. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015 Nov 5;373(19):1803-13. doi: 10.1056/NEJMoa1510665. Epub 2015 Sep 25.
2. Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, Rini BI, Hammers HJ, Donskov F, Roth BJ, Peltola K, Lee JL, Heng DYC, Schmidinger M, Agarwal N, Sternberg CN, McDermott DF, Aftab DT, Hessel C, Scheffold C, Schwab G, Hutson TE, Pal S, Motzer RJ; METEOR investigators. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016 Jul;17(7):917-927. doi: 10.1016/S1470-2045(16)30107-3. Epub 2016 Jun 5.