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Outcomes for International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Groups in Contemporary
Matthew S Ernst1, Vishal Navani1, J Connor Wells1
1Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada.
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.
Patient Summary:
The International Metastatic Renal Cell Carcinoma Database Consortium model continues to stratify patients with metastatic renal cell carcinoma receiving modern combination treatments in the real-world setting.
Insights
The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model effectively stratifies patients with metastatic renal cell carcinoma (mRCC) receiving first-line immuno-oncology (IO) therapies. This study provides crucial real-world survival benchmarks for these advanced mRCC treatments.
Area of Science:
- Oncology
- Clinical Research
- Cancer Treatment
Background:
- First-line treatments for metastatic renal cell carcinoma (mRCC) include ipilimumab and nivolumab (IPI-NIVO) and immuno-oncology (IO) plus vascular endothelial growth factor targeted therapies (IO-VEGF).
- Vascular endothelial growth factor targeted therapies (VEGF-TT) are also a standard treatment option.
Purpose of the Study:
- To establish real-world clinical benchmarks for IO combination therapies in mRCC.
- To validate the utility of the International mRCC Database Consortium (IMDC) criteria for stratifying patients receiving modern treatments.
Main Methods:
- Retrospective analysis of the IMDC database (2002-2021) including patients with mRCC who received first-line IPI-NIVO, IO-VEGF, or VEGF-TT.
- Patients were stratified according to IMDC risk groups.
- Overall survival (OS), time to next treatment (TTNT), and treatment duration (TD) were analyzed using Kaplan-Meier and log-rank tests. Overall response rate (ORR) was assessed.
Main Results:
- The IMDC model successfully stratified patients into distinct risk groups across all three treatment cohorts (IPI-NIVO, IO-VEGF, VEGF-TT) for OS, TTNT, and TD.
- Provided 18-month OS rates stratified by IMDC risk for each treatment, highlighting significant differences.
- Reported ORRs for favorable, intermediate, and poor-risk groups across the treatment modalities, with IO-VEGF showing higher response rates.
Conclusions:
- The IMDC risk stratification model remains relevant and effective for patients with mRCC treated with contemporary first-line IO combination therapies.
- The study provides valuable real-world survival benchmarks for IPI-NIVO, IO-VEGF, and VEGF-TT in the management of mRCC.
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