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Conference Paper: Prognostic and predictive blood-based biomarkers of overall survival (OS) in patients (pts) with advanced colorectal cancer (CRC) treated with cetuximab (C): Results from CALGB 80203 (Alliance)

TitlePrognostic and predictive blood-based biomarkers of overall survival (OS) in patients (pts) with advanced colorectal cancer (CRC) treated with cetuximab (C): Results from CALGB 80203 (Alliance)
Authors
Issue Date2014
PublisherLippincott Williams & Wilkins.
Citation
The 2014 Annual Meeting of the American Society of Clinical Oncology (ASCO 2014), Chicago, IL., 30 May-3 June 2014. In Journal of Clinical Oncology, 2014, v. 32 n. 15 suppl., abstract no. 11022 How to Cite?
AbstractBACKGROUND: Previously, we identified potential predictive biomarkers of C sensitivity related to EGFR signaling from archived tumor tissue from CALGB 80203. Due to the fact that blood-based markers are more convenient and can be monitored over the course of treatment, baseline plasma samples were also collected and five (EGF, HB-EGF, sEGFR, sHER2, sHER3) markers were evaluated in plasma. METHODS: CALGB 80203 was a randomized (1:1) phase II trial of 238 pts with locally advanced or metastatic CRC comparing FOLFOX or FOLFIRI (chemo) vs. chemo plus C. Baseline EDTA plasma samples from 154 pts were analyzed for the five candidate markers; an ELISA for CD73 is currently being optimized for use. The levels of each analyte were correlated with the primary endpoint of OS using univariate Cox proportional hazards models. Potential predictive markers were identified using a treatment by marker interaction term in the Cox model and the markers with significant p-values are reported. Hazard ratios between treatment groups are reported for low or high marker levels dichotomized at the median. RESULTS: Univariate analyses indicated that plasma levels of EGF and sHER3 were negative prognostic markers (p<0.05) that correlated with OS for the overall pt population. Across all pts (KRAS mutant and wild-type), sHER3 was identified as a potential predictive biomarker for C. Pts with higher sHER3 levels had significant OS benefit from C treatment (interaction p=0.03; HR=0.57, 95% CI 0.36-0.92). Low levels of EGF predicted for OS benefit from C in KRAS WT tumors (interaction p<0.01; HR=0.42, 95% CI 0.19-0.90) and lack of benefit in the KRAS mutant pts (interaction p=0.03; HR=2.69, 95% CI 1.04-6.94), but were not predictive for C across all pts. CONCLUSIONS: Blood-based profiling of EGFR axis members identified sHER3 and EGF as candidate predictors for benefit from C. These data are consistent with our findings using mRNA expression from archived tumor samples and suggest a role for receptor shedding in HER3 biology. If further validated, these markers may help guide the development and use of anti-EGFR therapies and combination regimens.
DescriptionThis journal suppl. entitled: 2014 ASCO Annual Meeting Abstracts
Persistent Identifierhttp://hdl.handle.net/10722/195793
ISSN
2015 Impact Factor: 20.982
2015 SCImago Journal Rankings: 9.204

 

DC FieldValueLanguage
dc.contributor.authorHatch, AJen_US
dc.contributor.authorPang, HMHen_US
dc.contributor.authorStarr, MDen_US
dc.contributor.authorBrady, JCen_US
dc.contributor.authorJia, Jen_US
dc.contributor.authorChen, Jen_US
dc.contributor.authorSibley, Aen_US
dc.contributor.authorOwzar, Ken_US
dc.contributor.authorNiedzwiecki, Den_US
dc.contributor.authorVenook, APen_US
dc.contributor.authorCushman, SM-
dc.contributor.authorHurwitz, H-
dc.contributor.authorNixon, AB-
dc.date.accessioned2014-03-10T04:53:31Z-
dc.date.available2014-03-10T04:53:31Z-
dc.date.issued2014en_US
dc.identifier.citationThe 2014 Annual Meeting of the American Society of Clinical Oncology (ASCO 2014), Chicago, IL., 30 May-3 June 2014. In Journal of Clinical Oncology, 2014, v. 32 n. 15 suppl., abstract no. 11022en_US
dc.identifier.issn0732-183Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/195793-
dc.descriptionThis journal suppl. entitled: 2014 ASCO Annual Meeting Abstracts-
dc.description.abstractBACKGROUND: Previously, we identified potential predictive biomarkers of C sensitivity related to EGFR signaling from archived tumor tissue from CALGB 80203. Due to the fact that blood-based markers are more convenient and can be monitored over the course of treatment, baseline plasma samples were also collected and five (EGF, HB-EGF, sEGFR, sHER2, sHER3) markers were evaluated in plasma. METHODS: CALGB 80203 was a randomized (1:1) phase II trial of 238 pts with locally advanced or metastatic CRC comparing FOLFOX or FOLFIRI (chemo) vs. chemo plus C. Baseline EDTA plasma samples from 154 pts were analyzed for the five candidate markers; an ELISA for CD73 is currently being optimized for use. The levels of each analyte were correlated with the primary endpoint of OS using univariate Cox proportional hazards models. Potential predictive markers were identified using a treatment by marker interaction term in the Cox model and the markers with significant p-values are reported. Hazard ratios between treatment groups are reported for low or high marker levels dichotomized at the median. RESULTS: Univariate analyses indicated that plasma levels of EGF and sHER3 were negative prognostic markers (p<0.05) that correlated with OS for the overall pt population. Across all pts (KRAS mutant and wild-type), sHER3 was identified as a potential predictive biomarker for C. Pts with higher sHER3 levels had significant OS benefit from C treatment (interaction p=0.03; HR=0.57, 95% CI 0.36-0.92). Low levels of EGF predicted for OS benefit from C in KRAS WT tumors (interaction p<0.01; HR=0.42, 95% CI 0.19-0.90) and lack of benefit in the KRAS mutant pts (interaction p=0.03; HR=2.69, 95% CI 1.04-6.94), but were not predictive for C across all pts. CONCLUSIONS: Blood-based profiling of EGFR axis members identified sHER3 and EGF as candidate predictors for benefit from C. These data are consistent with our findings using mRNA expression from archived tumor samples and suggest a role for receptor shedding in HER3 biology. If further validated, these markers may help guide the development and use of anti-EGFR therapies and combination regimens.-
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins.en_US
dc.relation.ispartofJournal of Clinical Oncologyen_US
dc.titlePrognostic and predictive blood-based biomarkers of overall survival (OS) in patients (pts) with advanced colorectal cancer (CRC) treated with cetuximab (C): Results from CALGB 80203 (Alliance)en_US
dc.typeConference_Paperen_US
dc.identifier.emailPang, HMH: herbpang@hku.hken_US
dc.identifier.authorityPang, HMH=rp01857en_US
dc.identifier.volume32en_US
dc.identifier.issue15 suppl. (May 20 Supplement)-
dc.publisher.placeUnited Statesen_US

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