IGF-Binding Proteins, Adiponectin, and Survival in Metastatic Colorectal Cancer: Results From CALGB (Alliance)/SWOG 80405.

Journal Article (Clinical Trial, Phase III;Journal Article)

Background: Energy balance-related biomarkers are associated with risk and prognosis of various malignancies. Their relationship to survival in metastatic colorectal cancer (mCRC) requires further study. Methods: Baseline plasma insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3, IGFBP-7, C-peptide, and adiponectin were measured at time of trial registration in a prospective cohort of patients with mCRC participating in a National Cancer Institute-sponsored trial of first-line systemic therapy. We used Cox proportional hazards regression to adjust for confounders and examine associations of each biomarker with overall survival (OS) and progression-free survival (PFS). P values are 2-sided. Results: Median follow-up for 1086 patients was 6.2 years. Compared with patients in the lowest IGFBP-3 quintile, patients in the highest IGFBP-3 quintile experienced an adjusted hazard ratio (HR) for OS of 0.57 (95% confidence interval [CI] = 0.42 to 0.78; P nonlinearity < .001) and for PFS of 0.61 (95% CI = 0.45 to 0.82; P trend = .003). Compared with patients in the lowest IGFBP-7 quintile, patients in the highest IGFBP-7 quintile experienced an adjusted hazard ratio for OS of 1.60 (95% CI = 1.30 to 1.97; P trend < .001) and for PFS of 1.38 (95% CI = 1.13 to 1.69; P trend < .001). Plasma C-peptide and IGF-1 were not associated with patient outcomes. Adiponectin was not associated with OS; there was a nonlinear U-shaped association between adiponectin and PFS (P nonlinearity = .03). Conclusions: Among patients with mCRC, high plasma IGFBP-3 and low IGFBP-7 were associated with longer OS and PFS. Extreme levels of adiponectin were associated with shorter PFS. These findings suggest potential avenues for prognostic and therapeutic innovation.

Full Text

Duke Authors

Cited Authors

  • Guercio, BJ; Zhang, S; Ou, F-S; Venook, AP; Niedzwiecki, D; Lenz, H-J; Innocenti, F; Pollak, MN; Nixon, AB; Mullen, BC; O'Neil, BH; Shaw, JE; Polite, BN; Benson, AB; Atkins, JN; Goldberg, RM; Brown, JC; O'Reilly, EM; Mayer, RJ; Blanke, CD; Fuchs, CS; Meyerhardt, JA

Published Date

  • February 2021

Published In

Volume / Issue

  • 5 / 1

PubMed ID

  • 33426464

Pubmed Central ID

  • PMC7785047

Electronic International Standard Serial Number (EISSN)

  • 2515-5091

Digital Object Identifier (DOI)

  • 10.1093/jncics/pkaa074


  • eng

Conference Location

  • England