Dynamic tumor modeling of the dose-response relationship for everolimus in metastatic renal cell carcinoma using data from the phase 3 RECORD-1 trial. Academic Article uri icon

Overview

abstract

  • BACKGROUND: The phase 3 RECORD-1 trial (NCT00410124) established the efficacy and safety of everolimus in patients with metastatic renal cell carcinoma (mRCC) who progress on sunitinib or sorafenib. In RECORD-1, patients received 10 mg everolimus daily, with dose reduction to 5 mg daily allowed for toxicity. We have developed a model of tumor growth dynamics utilizing serial measurements of the sum of the longest tumor diameters (SLD) from individual RECORD-1 patients to define the dose-response relationship of everolimus. RESULTS: The model predicts that after 1 year of continuous dosing, the change in SLD of target lesions will be +142.1% ± 98.3%, +22.4% ± 17.2%, and -15.7% ± 11.5% in the average patient treated with placebo, 5 mg everolimus, and 10 mg everolimus, respectively. This nonlinear, mixed-effects modeling approach can be used to describe the dynamics of each individual patient, as well as the overall population. This allows evaluation of how an actual dosing history and individual covariates impact on the observed drug effect, and offers the possibility of predicting clinical observations as a function of time. CONCLUSIONS: In this pharmacodynamic model of tumor response, everolimus more effectively shrinks target lesions in mRCC when dosed 10 mg daily versus 5 mg daily, although a 5-mg dose still shows an antitumor effect. These data support earlier studies that established 10 mg daily as the preferred clinical dose of everolimus, and improve our understanding of the everolimus dose-response relationship.

publication date

  • July 23, 2012

Research

keywords

  • Antineoplastic Agents
  • Carcinoma, Renal Cell
  • Kidney Neoplasms
  • Models, Biological
  • Sirolimus

Identity

PubMed Central ID

  • PMC3495014

Scopus Document Identifier

  • 84868682369

Digital Object Identifier (DOI)

  • 10.1016/j.ejca.2011.02.014

PubMed ID

  • 22824201

Additional Document Info

volume

  • 12