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Updated: May 20, 2026

A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
06:38

A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies

Published on: April 12, 2017

Dynamic tumor modeling of the dose-response relationship for everolimus in metastatic renal cell carcinoma using data

Andrew Stein1, Wenping Wang, Alison A Carter

  • 1Modeling & Simulation, Novartis Institutes for Biomedical Research, 45 Sidney St, Cambridge, MA, USA. andrew.stein@novartis.com

BMC Cancer
|July 25, 2012
PubMed
Abstract

Insights

Everolimus at 10mg daily showed superior tumor shrinkage in metastatic renal cell carcinoma (mRCC) patients compared to 5mg daily. This study models everolimus dose-response for mRCC treatment.

Area of Science:

  • Pharmacodynamics
  • Oncology
  • Clinical Trial Analysis

Background:

  • The RECORD-1 trial evaluated everolimus for metastatic renal cell carcinoma (mRCC) post-sunitinib or sorafenib progression.
  • Patients received 10mg daily everolimus, with a 5mg daily option for toxicity management.
  • A tumor growth dynamics model was developed using sum of longest diameters (SLD) from RECORD-1 data.

Purpose of the Study:

  • To define the dose-response relationship of everolimus in mRCC patients.
  • To model tumor growth dynamics and predict treatment outcomes based on everolimus dosage.

Main Methods:

  • Utilized serial measurements of sum of longest tumor diameters (SLD) from individual patients in the RECORD-1 trial.
  • Developed a nonlinear, mixed-effects modeling approach to analyze tumor growth dynamics.
  • Modeled individual patient responses and overall population dynamics to assess dose-response relationships.

Main Results:

  • The model predicts a 1-year change in SLD of -15.7% with 10mg everolimus, +22.4% with 5mg everolimus, and +142.1% with placebo.
  • Demonstrated that the modeling approach can describe individual patient dynamics and overall population response.
  • Showcased the ability to evaluate the impact of dosing history and covariates on drug effect and predict clinical outcomes over time.

Conclusions:

  • Everolimus at 10mg daily demonstrated greater efficacy in shrinking target lesions in mRCC compared to 5mg daily.
  • A 5mg daily dose of everolimus still exhibited an antitumor effect in mRCC patients.
  • These findings support the established 10mg daily dose as preferred and enhance understanding of everolimus pharmacodynamics in mRCC.

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