ASCO GU 2022: Characterizing IMDC Prognostic Groups in Contemporary First-Line Combination Therapies for mRCC

(UroToday.com) The 2022 GU ASCO Annual meeting included a renal cell carcinoma (RCC) session highlighting work from Dr. Matthew Ernst and colleagues presenting results characterizing the International Metastatic RCC Database Consortium (IMDC) prognostic groups in contemporary first-line combination therapies for metastatic RCC. The combination of immuno-oncology agents (IO) ipilimumab and nivolumab and combinations of IO with vascular endothelial growth factor targeted therapy (VEGF-TT) have demonstrated efficacy in clinical trials for the first-line treatment of metastatic RCC. This study seeks to establish real-world clinical benchmarks based on the IMDC criteria using VEGF-TT treated patients for context.


The IMDC database (IMDConline.com) was used to identify patients with metastatic RCC who received first-line ipilimumab and nivolumab, IO with vascular endothelial growth factor targeted therapy (axitinib/pembrolizumab, lenvatinib/pembrolizumab, cabozantinib/nivolumab, or axitinib/avelumab), and VEGF-TT (sunitinib or pazopanib) from 2002-2021. The primary endpoint was overall survival (OS) and was calculated from time of initiation of first-line therapy to death or last follow up. Log-rank tests were conducted to compare favorable, intermediate, and poor risk OS outcomes within treatment groups. Overall response rates (ORR) and complete response (CR) rates were calculated based on physician assessment of best clinical response.

 In total, 692 patients received ipilimumab and nivolumab, 244 received IO with VEGF-TT, and 7,152 received VEGF-TT. Baseline characteristics for ipilimumab and nivolumab, IO with VEGF-TT, and VEGF-TT, respectively, were as follows:

  • Median age 63 (IQR 56-69) years, 64 (IQR 57-70) years, and 63 (IQR 56-70) years
  • Male 72%, 74%, and 72% (p=0.74)
  • Non-clear cell histology 15%, 10%, and 13% (p=0.15)
  • Sarcomatoid features 24%, 15%, and 13% (p<0.0001)
  • Brain metastasis 8%, 4%, and 8% (p=0.04)
  • Liver metastasis 18%, 14%, and 18% (p=0.17)
  • Underwent nephrectomy 61%, 79% and 80% (p<0.0001)

The OS and ORR efficacy results, stratified by Nivolumab + ipilimumab, IO and VEGF-TT, and VEGF-TT are as follows:

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OS between risk groups were significant for ipilimumab and nivolumab (p<0.0001)

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OS between risk groups were also significant for IO with VEGF-TT (p=0.0005):

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Furthermore, OS between risk groups were significant for VEGF-TT (p<0.0001): 

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Dr. Ernst concluded his presentation of characterizing IMDC prognostic groups in contemporary first-line combination therapies for metastatic RCC with the following take-home messages:

  • These findings provide real-world survival and response benchmarks for contemporary first-line metastatic RCC treatments and could be helpful for patient counseling
  • In addition, these findings mirror the efficacy of combination therapies established in clinical trials against VEGF-TT monotherapy
  • IMDC criteria continue to risk stratify patients in these novel combination therapies

Presented by: Matthew S. Ernst, MD, Tom Baker Cancer Center, University of Calgary, Calgary, AB, Canada

Co-Authors: Vishal Navani, J Connor Wells, Frede Donskov, Naveen S. Basappa, Chris Labaki, Sumanta K. Pal, Luis A Meza, Lori Wood, D. Scott Ernst, Bernadett Szabados, Rana R. McKay, Francis Parnis, Cristina Suárez, Takeshi Yuasa, Anil Kapoor, Ajjai Shivaram Alva, Georg A. Bjarnason, Toni Choueiri, Daniel Yick Chin Heng

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022 

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