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Article: Blood-based markers of efficacy and resistance to cetuximab treatment in metastatic colorectal cancer: results from CALGB 80203 (Alliance)

TitleBlood-based markers of efficacy and resistance to cetuximab treatment in metastatic colorectal cancer: results from CALGB 80203 (Alliance)
Authors
KeywordsBiomarker
cetuximab
colorectal cancer
plasma
Issue Date2016
PublisherWiley Open Access. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2045-7634
Citation
Cancer Medicine, 2016, v. 5 n. 9, p. 2249-2260 How to Cite?
AbstractCirculating protein markers were assessed in patients with colorectal cancer (CRC) treated with cetuximab in CALGB 80203 to identify prognostic and predictive biomarkers. Patients with locally advanced or metastatic CRC received FOLFOX or FOLFIRI chemotherapy (chemo) or chemo in combination with cetuximab. Baseline plasma samples from 152 patients were analyzed for six candidate markers [epidermal growth factor (EGF), heparin‐binding EGF (HBEGF), epidermal growth factor receptor (EGFR), HER2, HER3, and CD73]. Analyte levels were associated with survival endpoints using univariate Cox proportional hazards models. Predictive markers were identified using a treatment‐by‐marker interaction term in the Cox model. Plasma levels of EGF, HBEGF, HER3, and CD73 were prognostic for overall survival (OS) across all patients (KRAS mutant and wild‐type). High levels of EGF predicted for lack of OS benefit from cetuximab in KRAS wild‐type (WT) patients (chemo HR = 0.98, 95% CI = 0.74–1.29; chemo+cetuximab HR = 1.54, 95% CI = 1.05–2.25; interaction P = 0.045) and benefit from cetuximab in KRAS mutant patients (chemo HR = 1.72, 95% CI = 1.02–2.92; chemo+cetuximab HR = 0.90, 95% CI = 0.67–1.21; interaction P = 0.026). Across all patients, higher HER3 levels were associated with significant OS benefit from cetuximab treatment (chemo HR = 4.82, 95% CI = 1.68–13.84; chemo+cetuximab HR = 0.95, 95% CI = 0.31–2.95; interaction P = 0.046). CD73 was also identified as predictive of OS benefit in KRAS WT patients (chemo HR = 1.28, 95% CI = 0.88–1.84; chemo+cetuximab HR = 0.60, 95% CI = 0.32–1.13; interaction P = 0.049). Although these results are preliminary, and confirmatory studies are necessary before clinical application, the data suggest that HER3 and CD73 may play important roles in the biological response to cetuximab.
Persistent Identifierhttp://hdl.handle.net/10722/281772
ISSN
2020 Impact Factor: 4.452
2020 SCImago Journal Rankings: 1.403
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHatch, AJ-
dc.contributor.authorSibley, AB-
dc.contributor.authorStarr, MD-
dc.contributor.authorBrady, JC-
dc.contributor.authorJiang, C-
dc.contributor.authorJia, J-
dc.contributor.authorBowers, DL-
dc.contributor.authorPang, H-
dc.contributor.authorOwzar, K-
dc.contributor.authorNiedzwiecki, D-
dc.contributor.authorInnocenti, F-
dc.contributor.authorVenook, AP-
dc.contributor.authorHurwitz, HI-
dc.contributor.authorNixon, AB-
dc.contributor.authorThe Alliance for Clinical Trials in Oncology-
dc.date.accessioned2020-03-27T04:22:21Z-
dc.date.available2020-03-27T04:22:21Z-
dc.date.issued2016-
dc.identifier.citationCancer Medicine, 2016, v. 5 n. 9, p. 2249-2260-
dc.identifier.issn2045-7634-
dc.identifier.urihttp://hdl.handle.net/10722/281772-
dc.description.abstractCirculating protein markers were assessed in patients with colorectal cancer (CRC) treated with cetuximab in CALGB 80203 to identify prognostic and predictive biomarkers. Patients with locally advanced or metastatic CRC received FOLFOX or FOLFIRI chemotherapy (chemo) or chemo in combination with cetuximab. Baseline plasma samples from 152 patients were analyzed for six candidate markers [epidermal growth factor (EGF), heparin‐binding EGF (HBEGF), epidermal growth factor receptor (EGFR), HER2, HER3, and CD73]. Analyte levels were associated with survival endpoints using univariate Cox proportional hazards models. Predictive markers were identified using a treatment‐by‐marker interaction term in the Cox model. Plasma levels of EGF, HBEGF, HER3, and CD73 were prognostic for overall survival (OS) across all patients (KRAS mutant and wild‐type). High levels of EGF predicted for lack of OS benefit from cetuximab in KRAS wild‐type (WT) patients (chemo HR = 0.98, 95% CI = 0.74–1.29; chemo+cetuximab HR = 1.54, 95% CI = 1.05–2.25; interaction P = 0.045) and benefit from cetuximab in KRAS mutant patients (chemo HR = 1.72, 95% CI = 1.02–2.92; chemo+cetuximab HR = 0.90, 95% CI = 0.67–1.21; interaction P = 0.026). Across all patients, higher HER3 levels were associated with significant OS benefit from cetuximab treatment (chemo HR = 4.82, 95% CI = 1.68–13.84; chemo+cetuximab HR = 0.95, 95% CI = 0.31–2.95; interaction P = 0.046). CD73 was also identified as predictive of OS benefit in KRAS WT patients (chemo HR = 1.28, 95% CI = 0.88–1.84; chemo+cetuximab HR = 0.60, 95% CI = 0.32–1.13; interaction P = 0.049). Although these results are preliminary, and confirmatory studies are necessary before clinical application, the data suggest that HER3 and CD73 may play important roles in the biological response to cetuximab.-
dc.languageeng-
dc.publisherWiley Open Access. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2045-7634-
dc.relation.ispartofCancer Medicine-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectBiomarker-
dc.subjectcetuximab-
dc.subjectcolorectal cancer-
dc.subjectplasma-
dc.titleBlood-based markers of efficacy and resistance to cetuximab treatment in metastatic colorectal cancer: results from CALGB 80203 (Alliance)-
dc.typeArticle-
dc.identifier.emailPang, H: herbpang@hku.hk-
dc.identifier.authorityPang, H=rp01857-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1002/cam4.806-
dc.identifier.pmid27465221-
dc.identifier.pmcidPMC5055181-
dc.identifier.scopuseid_2-s2.0-84989244695-
dc.identifier.hkuros309588-
dc.identifier.volume5-
dc.identifier.issue9-
dc.identifier.spage2249-
dc.identifier.epage2260-
dc.identifier.isiWOS:000385355500010-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl2045-7634-

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