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Updated: Oct 15, 2025
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Overall survival improvement in patients with metastatic clear-cell renal cell carcinoma between 2000 and 2020: a
Sofie Demasure1, Isabel Spriet2, Philip R Debruyne3
1Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium.
Background:
Only a few recent phase III trials with targeted therapies or immune checkpoint inhibitors (ICIs) in metastatic clear-cell renal cell carcinoma (m-ccRCC) demonstrated an overall survival (OS) benefit compared to standard of care. We aimed to study the evolution of OS since the start of systemic therapy from 2000 to 2020.
Patients And Methods:
Retrospective study on all consecutively treated m-ccRCC patients in three Belgian hospitals starting with systemic therapy. The study outcome was OS since the start of systemic therapy. We used a univariable Cox model for OS with year of the start of therapy as a predictor, and a multivariable analysis including known prognostic factors. Linear and non-linear trends of time were tested.
Results:
Five hundred patients were included. In a linear model, the HR for OS depending on the year of the start of therapy was 0.95 (95%CI 0.93-0.97; p < 0.0001), estimated for an increase with 1 year in time. In a non-linear model, OS started to improve from 2006 on, when vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) replaced interferon alfa (IFNa) as a standard of care and continued to increase steadily during the following years. On multivariable analysis, the year of the start of therapy remained an independent prognostic factor for OS. Two-year OS after the start of systemic therapy was 23%, 34%, 50% and 59% for patients who started treatment in 2000-2005, 2006-2011, 2012-2017, and 2018-2020, respectively. The five-year OS of the first three groups was 7%, 14% and 24%. The mean number of administered lines of therapy increased over time, with an incidence rate ratio of 1.07 (95%CI 1.05-1.08; p < 0.0001) per year increase for the period 2000-2016.
Conclusion:
OS of m-ccRCC patients has been improving significantly over the last 15 years since the introduction of VEGFR-TKIs and ICIs.
Insights
Overall survival for metastatic clear-cell renal cell carcinoma (m-ccRCC) patients has significantly improved since 2006. This improvement is linked to the introduction of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) and immune checkpoint inhibitors (ICIs).
Area of Science:
- Oncology
- Medical Research
Background:
- Metastatic clear-cell renal cell carcinoma (m-ccRCC) treatment has seen limited overall survival (OS) benefits from recent targeted therapies and immune checkpoint inhibitors (ICIs).
- The evolution of OS in m-ccRCC patients receiving systemic therapy from 2000 to 2020 requires investigation.
Purpose of the Study:
- To analyze the trend of overall survival (OS) in metastatic clear-cell renal cell carcinoma (m-ccRCC) patients since the initiation of systemic therapy.
- To determine the impact of therapeutic advancements on OS over a two-decade period.
Main Methods:
- A retrospective analysis of 500 consecutively treated m-ccRCC patients across three Belgian hospitals.
- Utilized univariable and multivariable Cox models to assess the impact of the therapy start year on OS, controlling for known prognostic factors.
- Investigated both linear and non-linear trends in OS over time.
Main Results:
- A significant linear improvement in OS was observed, with a hazard ratio of 0.95 per year increase in therapy start date (p < 0.0001).
- OS began to notably improve from 2006, coinciding with the shift from interferon alfa (IFNα) to vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs).
- Two-year OS rates increased from 23% (2000-2005) to 59% (2018-2020), and five-year OS improved from 7% to 24% in the same periods.
Conclusions:
- Overall survival for m-ccRCC patients has markedly improved over the past 15 years.
- The introduction and widespread use of VEGFR-TKIs and ICIs are key drivers of this enhanced survival.
- The year of therapy initiation remains an independent prognostic factor for OS in m-ccRCC.
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