@article{d9cb5d8b3c074d5fadc7502acc785ea3,
title = "IGF-Binding Proteins, Adiponectin, and Survival in Metastatic Colorectal Cancer: Results from CALGB (Alliance)/SWOG 80405",
abstract = "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; Pnonlinearity < .001) and for PFS of 0.61 (95% CI = 0.45 to 0.82; Ptrend = .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; Ptrend < .001) and for PFS of 1.38 (95% CI = 1.13 to 1.69; Ptrend < .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 (Pnonlinearity = .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.",
author = "Guercio, {Brendan J.} and Sui Zhang and Ou, {Fang Shu} and Venook, {Alan P.} and Donna Niedzwiecki and Lenz, {Heinz Josef} and Federico Innocenti and Pollak, {Michael N.} and Nixon, {Andrew B.} and Mullen, {Brian C.} and O'Neil, {Bert H.} and Shaw, {James E.} and Polite, {Blase N.} and {Al Bowen}, Benson and Atkins, {James N.} and Goldberg, {Richard M.} and Brown, {Justin C.} and O'Reilly, {Eileen M.} and Mayer, {Robert J.} and Blanke, {Charles D.} and Fuchs, {Charles S.} and Meyerhardt, {Jeffrey A.}",
note = "Funding Information: U54GM104940 to JCB); the Stand-Up-to-Cancer Colorectal Dream Team Grant to CSF; the Guo Shu Shi Fund to JAM; the Karen Guo Colon Cancer Research Fund to JAM; the Stone Research Fund to JAM; the Douglas Gray Woodruff Chair Fund to JAM; Eli Lily & Company; Genentech; Pfizer; Sanofi; and supporters of the Alliance for Clinical Trials in Oncology and Alliance Foundation Trials programs, as detailed at https://acknowledgments.alliancefound.org. Funding Information: Disclosures: BJG has conducted research associated with institutional funding from Bristol-Myers Squibb, Genentech, Eli Lily, Pfizer, and Sanofi and has received honoraria from Medscape. JAM has received institutional research funding from Boston Biomedical and has served as an advisor/consultant to COTA Healthcare and served on a grant review panel for the National Comprehensive Cancer Network funded by Taiho Pharmaceutical. APV has served as an advisor/consultant for Taiho Pharmaceutical, Bayer, Halozyme, and Eisai; has received institutional research funding from Genentech and Bristol-Myers Squibb; has received royalties from Now-UptoDate for authoring and maintaining 2 chapters; and has received travel, accommodations, or other expenses from Genentech, Roche, Halozyme, and Bayer. HJL has served as an advisor/consultant to Merck Serono, Roche, Bayer, and Pfizer; has received honoraria from Merck Serono, Roche, Bayer, and Boehringer Ingelheim; and has received travel, accommodations, or other expenses from Merck Serono, Bayer, and Roche. BHO has been employed by Eli Lilly and has served as an advisor/consultant to Bristol-Myers Squibb and Merck. BNP has received research funding from Merck; has received travel, accommodations, or other expenses from Tapestry Pharmaceuticals; and has other relationships with Gerson Lehrman Group. RMG has served as an advisor/consultant to Merck, Taiho Pharmaceutical, Merck, and Novartis; has received research funding from Bristol-Myers Squibb; has received honoraria from Amgen; and has received travel, accommodations, or other expenses from Merck and Amgen. EOR has received institutional research funding from Genentech, BMS, Halozyme, Celgene, MabVax Therapeutics, ActaBiologica, AstraZeneca, Silenseed, and Polaris and has served as an advisor/consultant to CytomX Therapeutics, BioLineRx, Targovax, Ipsen, Celgene, Bayer, Polaris, Sobi, and Merck. CSF has served in a leadership role for CytomX Therapeutics; has stock or other ownership interests in CytomX Therapeutics and Entrinsic Health; and has served as an advisor/consultant to Eli Lilly, Sanofi, Merck, Entrinsic Health, Agios, Merrimack Pharmaceuticals, Taiho Pharmaceutical, Genentech, CytomX Therapeutics, Unum Therapeutics, Bain Capital, Bayer, Gilead Sciences, Dicerna, Five Prime Therapeutics, KEW, Celgene, and Pfizer. The remaining authors declare no potential conflicts of interest. Funding Information: This work was supported by the National Cancer Institute of the National Institutes of Health (grant numbers U10CA180821 and U10CA180882 to the Alliance for Clinical Trials in Oncology; U10CA180857, U10CA180790, U10CA180791, U10CA180795, U10CA180826, U10CA180836, U10CA180838, U10CA180867, and UG1CA189858; U10CA180820 to ECOG-ACRIN; U10CA180888 and U10CA180830 to SWOG; R01 CA169141 and R01 CA118553 to CSF; R01CA149222 to JAM; R00CA218603 and R25CA203650 to JCB); the National Institute of General Medicine Sciences of the National Institutes of Health (grant number Publisher Copyright: {\textcopyright} 2021 Oxford University Press. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
doi = "10.1093/JNCICS/PKAA074",
language = "English (US)",
volume = "5",
journal = "JNCI Cancer Spectrum",
issn = "2515-5091",
publisher = "Oxford University Press",
number = "1",
}