Outcomes for International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Groups in Contemporary First-line Combination Therapies for Metastatic Renal Cell Carcinoma

Background: The combination of immuno-oncology (IO) agents ipilimumab and nivolumab (IPI-NIVO) and vascular endothelial growth factor targeted therapies (VEGF-TT) combined with IO (IO-VEGF) are current standard of care first-line treatments for metastatic renal cell carcinoma (mRCC).

Objective: To establish real-world clinical benchmarks for IO combination therapies based on the International mRCC Database Consortium (IMDC) criteria.

Design, setting, and participants: Patients with mRCC who received first-line IPI-NIVO, IO-VEGF, or VEGF-TT from 2002 to 2021 were identified using the IMDC database and stratified according to IMDC risk groups.

Outcome measurements and statistical analysis: Overall survival (OS), time to next treatment (TTNT), and treatment duration (TD) were calculated using the Kaplan-Meier method and compared between IMDC risk groups within each treatment cohort by the log-rank test. The overall response rate (ORR) was calculated by physician assessment of the best overall response. The primary outcome was OS at 18 mo.

Results and limitations: In total, 728 patients received IPI-NIVO, 282 IO-VEGF, and 7163 VEGF-TT. The median follow-up times for patients remaining alive were 14.3 mo for IPI-NIVO, 14.9 mo IO-VEGF, and 34.4 mo for VEGF-TT. OS at 18 mo for favorable, intermediate, and poor risk was, respectively, 90%, 78%, and 50% for those receiving IPI-NIVO; 93%, 83%, and 74% for IO-VEGF; and 84%, 64%, and 28% for VEGF-TT. ORRs in favorable-, intermediate-, and poor-risk groups were 41.3%, 40.6%, and 33.0% for those receiving IPI-NIVO; 60.3%, 56.8%, and 40.9% for IO-VEGF; and 39.3%, 33.5%, and 20.9% for VEGF-TT, respectively. The IMDC model stratified patients into statistically distinct risk groups for the three endpoints of OS, TTNT, and TD within each treatment cohort. Limitations of this study were the retrospective design and short follow-up.

Conclusions: This study demonstrated that the IMDC model continues to risk stratify patients with mRCC treated with contemporary first-line IO combination therapies and provided real-world survival benchmarks.

Matthew S. Ernst, Vishal Navani, J. Connor Wells, Frede Donskov, Naveen Basappa, Chris Labaki, Sumanta K. Pal, Luis Meza, Lori A. Wood, D. Scott Ernst, Bernadett Szabados, Rana R. McKay, Francis Parnis, Cristina Suarez, Takeshi Yuasa, Aly-Khan Lalani, Ajjai Alva, Georg A. Bjarnason, Toni K. Choueiri, Daniel Y.C. Heng

Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Oncology, Aarhus University Hospital & University Hospital of Southern Denmark, Esbjerg, Denmark; Cross Cancer Clinic, University of Alberta, Edmonton, Alberta, Canada; Dana-Farber Cancer Institute, Boston, MA, USA; City of Hope Comprehensive Cancer Center, Duarte, CA, USA; Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada; London Regional Cancer Centre, London, Ontario, Canada; Barts Cancer Institute, Queen Mary University of London, London, UK; University of California San Diego, Moores Cancer Center, San Diego, CA, USA; Icon Cancer Centre, Adelaide, South Australia; Vall d’Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain; Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan; Juravinski Cancer Centre, McMaster University, Hamilton, Ontario, Canada; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada

Source: Ernst M. et al. Outcomes for International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Groups in Contemporary First-line Combination Therapies for Metastatic Renal Cell Carcinoma. European Urology Focus. 2023. ISSN 2405-4569.