title: Biomarker signatures correlate with clinical outcome in refractory metastatic colorectal cancer patients receiving bevacizumab and everolimus.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Yingmiao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Starr
authors.affiliation: Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, North Carolina.
authors.forename: John C
authors.initials: JC
authors.lastname: Brady
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina.
authors.forename: Christel
authors.initials: C
authors.lastname: Rushing
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Bulusu
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina. School of Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Herbert
authors.initials: H
authors.lastname: Pang
authors.affiliation: Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Wanda
authors.initials: W
authors.lastname: Honeycutt
authors.affiliation: Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Anthony
authors.initials: A
authors.lastname: Amara
authors.affiliation: Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Ivy
authors.initials: I
authors.lastname: Altomare
authors.affiliation: Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Hope E
authors.initials: HE
authors.lastname: Uronis
authors.affiliation: Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Herbert I
authors.initials: HI
authors.lastname: Hurwitz
authors.affiliation: Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, North Carolina. anixon@duke.edu.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Nixon
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000068338:Everolimus / Q000008:administration & dosage; D006801:Humans; D009362:Neoplasm Metastasis; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D000068258:Bevacizumab; D000068338:Everolimus