Biomarker signatures correlate with clinical outcome in refractory metastatic colorectal cancer patients receiving bevacizumab and everolimus.

Published

Journal Article

A novel combination of bevacizumab and everolimus was evaluated in refractory colorectal cancer patients in a phase II trial. In this retrospective analysis, plasma samples from 49 patients were tested for over 40 biomarkers at baseline and after one or two cycles of drug administration. Analyte levels at baseline and change on-treatment were correlated with progression-free survival (PFS) and overall survival (OS) using univariate Cox proportional hazard modeling. Multivariable analyses were conducted using Cox modeling. Significant changes in multiple markers were observed following bevacizumab and everolimus treatment. Baseline levels of six markers significantly correlated with PFS and OS, including CRP, Gro-α, IGFBP-1, TF, ICAM-1, and TSP-2 (P < 0.05). At C2D1, changes of IGFBP-3, TGFβ-R3, and IGFBP-2 correlated with PFS and OS. Prognostic models were developed for OS and PFS (P = 0.0002 and 0.004, respectively). The baseline model for OS consisted of CRP, Gro-α, and TF, while the on-treatment model at C2D1 included IGFBP-2, IGFBP-3, and TGFβ-R3. These data demonstrated that multiple biomarkers were significantly modulated in response to bevacizumab and everolimus. Several markers correlated with both PFS and OS. Interestingly, these markers are known to be associated with inflammation and IGF signaling, key modulators of mTOR biology.

Full Text

Duke Authors

Cited Authors

  • Liu, Y; Starr, MD; Brady, JC; Rushing, C; Bulusu, A; Pang, H; Honeycutt, W; Amara, A; Altomare, I; Uronis, HE; Hurwitz, HI; Nixon, AB

Published Date

  • April 2015

Published In

Volume / Issue

  • 14 / 4

Start / End Page

  • 1048 - 1056

PubMed ID

  • 25695956

Pubmed Central ID

  • 25695956

Electronic International Standard Serial Number (EISSN)

  • 1538-8514

Digital Object Identifier (DOI)

  • 10.1158/1535-7163.MCT-14-0923-T

Language

  • eng

Conference Location

  • United States