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Expression of drug targets in patients treated with sorafenib, carboplatin and paclitaxel

Lucia B Jilaveanu1, Fengmin Zhao, Christopher R Zito

  • 1Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut, United States of America.

Plos One
|August 13, 2013
PubMed
Abstract

Insights

High expression of FGF-R1 and VEGF-R1 correlated with better survival and response to carboplatin/paclitaxel therapy, suggesting potential predictive biomarkers for this regimen.

Area of Science:

  • Oncology
  • Molecular Biology
  • Clinical Trial Analysis

Background:

  • Sorafenib is a multitarget kinase inhibitor impacting MAPK and VEGFR pathways.
  • The study investigated sorafenib targets as biomarkers for taxane sensitivity and treatment response.
  • ECOG 2603 trial compared sorafenib, carboplatin, and paclitaxel (SCP) versus carboplatin, paclitaxel, and placebo (CP).

Purpose of the Study:

  • To assess the association between sorafenib target expression and patient response to therapy.
  • To identify potential predictive biomarkers for taxane-based chemotherapy in cancer treatment.
  • To evaluate the role of specific kinase expressions in treatment outcomes.

Main Methods:

  • Automated quantitative analysis (AQUA) of in situ protein expression was utilized.
  • Expression levels of 15 key proteins including VEGF-R1, VEGF-R2, FGF-R1, and MAPK pathway components were quantified.
  • Pre-treatment tumor specimens from 263 patients in the ECOG 2603 trial were analyzed.

Main Results:

  • High expression of Fibroblast Growth Factor Receptor 1 (FGF-R1) and Vascular Endothelial Growth Factor Receptor 1 (VEGF-R1) was associated with increased progression-free survival (PFS) and overall survival (OS).
  • Patients with higher FGF-R1 and VEGF-R1 expression showed better response rates (CR+PR) compared to those with lower expression.
  • No significant treatment effect was observed for sorafenib itself in this context.

Conclusions:

  • FGF-R1 and VEGF-R1 expression may serve as predictive biomarkers for carboplatin/paclitaxel-based therapy, independent of sorafenib's effect.
  • These findings suggest a potential strategy to optimize the therapeutic ratio of carboplatin and paclitaxel regimens.
  • Further validation in an independent cohort is recommended to confirm the predictive value of these biomarkers.

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