Primary Tumor Site and Anti-EGFR Monoclonal Antibody Benefit in Metastatic Colorectal Cancer: A Meta-Analysis

Li, Dandan; Fu, Qiang; Li, Man; Jun, Li; Yin, Can; Zhao, Jin; Li, Feng

doi:10.2217/fon-2016-0468

Cited by 9 publications

(7 citation statements)

References 43 publications

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“…This possibly explains the much better predictive performance of EGFR-HS detected in metastases. A multivariate analysis indicated that the EGFR protein expression of both the primary as well as the metastatic tissues is not an independent predictor of cetuximab efficacy unlike sidedness, confirming previous reports [17,18]. However, sidedness is not an EGFR-independent factor since it was shown recently that there is a close connection between EGFR protein expression and sidedness [11,19]: the poorly responding right-sided tumors express EGFR at significantly higher levels as compared to those left-sided [11].…”

Section: Discussionsupporting

confidence: 78%

“…Fortunately, strong negative predictors of the efficacy of anti-EGFR antibody therapies have been discovered: first KRAS exon2-, then rare KRAS-and NRAS mutations, and more recently BRAF mutations, the use of which improved patient selection for therapy [14][15][16]. Furthermore, it was also recently discovered that left-sided colorectal cancers respond significantly better to anti-EGFR therapies than do right-sided colorectal cancers [17,18]. Data also demonstrated that there is a difference in EGFR protein expression between left-and right-sided colorectal cancers that is independent from the RAS mutation statuses [11,19].…”

Section: Introductionmentioning

confidence: 99%

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EGFR Protein Expression in KRAS Wild-Type Metastatic Colorectal Cancer Is Another Negative Predictive Factor of the Cetuximab Therapy

Uhlyarik

Piurkó

Pápai

et al. 2020

Cancers

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The selection of colorectal cancer patients for anti-epidermal growth factor receptor (EGFR) antibody therapy is based on the determination of their RAS mutation status-a strongly negative predictive factor-since the protein target, EGFR, is not a reliable predictor of therapeutic response. In this study, we revisited the EGFR protein issue using a cohort of 90 patients with KRAS exon2 wild-type colorectal cancer who have been treated with cetuximab therapy. Twenty-nine of these patients had metastatic tissue available for analysis. The level of EGFR protein expression in the patients was determined by immunohistochemistry and evaluated by H-score (HS) methodology. Progression-free survival (PFS) and overall survival (OS) of the patients were determined according to the EGFR-HS ranges of both the primary and metastatic tissues using Kaplan-Meyer statistics. In the case of primary tumors, EGFR scores lower than HS = 200 were associated with significantly longer OS. In the case of metastatic tissues, all levels lower than the EGFR-HS range chosen were associated with significantly longer OS. These results are explained by the fact that metastatic tissues rarely maintained the expression levels of the primary tumors. On the other hand, high EGFR expression levels in either primary tumors or metastatic tissues were associated with multiple metastatic disease. This suggests a negative prognostic role of EGFR expression. However, in a multivariate analysis, one-sidedness remained a strong independent predictive factor of survival. Previous studies demonstrated that the EGFR expression level depends on sidedness. Therefore, a subgroup analysis of the left-and right-sided cases was performed on both primary and metastatic tissues. In the case of metastic tissues, an analysis confirmed a better OS in low EGFR protein-expressing cases than in high EGFR protein-expressing cases. Collectively, these data suggest that EGFR protein expression is another negative predictive factor of the efficacy of cetuximab therapy of KRAS exon2 wild-type colorectal cancer.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

EGFR Protein Expression in KRAS Wild-Type Metastatic Colorectal Cancer Is Another Negative Predictive Factor of the Cetuximab Therapy

Uhlyarik

Piurkó

Pápai

et al. 2020

Cancers

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“…On the other hand, an increasing number of studies reported that colon cancer can be divided according to distal and proximal colon cancer (26–28). Our research did not detect a difference between colon cancer in the left and right colons.…”

Section: Discussionmentioning

confidence: 99%

Prognostic lncRNAs, miRNAs, and mRNAs Form a Competing Endogenous RNA Network in Colon Cancer

Huang

Pan

2019

Front. Oncol.

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Purpose: To develop a multi-RNA-based model to provide survival risk prediction for colon cancer by constructing a competing endogenous RNAs (ceRNAs) network. Methods: The prognostic information and expression of the lncRNAs, miRNAs, and mRNAs in colon cancer specimens from The Cancer Genome Atlas (TCGA) were assessed. Constructing prognostic models used the differentially expressed RNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and Gene Ontology were used to identify the functional role of the ceRNA network in the prognosis of colon cancer. Results: Five lncRNAs (AC007384.1, AC002511.1, AC012640.1, C17orf82, and AP001619.1), 8 miRNAs (hsa-mir-141, hsa-mir-150, hsa-mir-375, hsa-mir-96, hsa-mir-107, hsa-mir-106a, hsa-mir-200a, and hsa-mir-1271), and 5 mRNAs (BDNF, KLF4, SESN2, SMOC1, and TRIB3) were highly correlated with tumor status and tumor stage. Three prognostic models based on the 5 lncRNAs, 8 miRNAs, and 5 mRNAs were constructed. The prognostic ability was 0.850 for the lncRNA-based model, 0.811 for the miRNA-based model, and 0.770 for the mRNA-based model. Patients with high-risk scores revealed worse overall survival. The KEGG pathways were significantly enriched in the “neuroactive ligand-receptor interaction.” Conclusion: This study identified several potential prognostic biomarkers to construct a multi-RNA-based prognostic model for colon cancer.

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“…Li et al 37 published a meta-analysis of primary tumour site and anti-egfr mAb benefit in mcrc. The analysis of the prognostic value of ptl included eleven studies, but the analysis of the predictive effect was limited to just two randomized controlled trials (crystal and ncic co.17).…”

Section: Meta-analyses Of the Effect Of Ptlmentioning

confidence: 99%

“…In addition, although most trials defined lcc as beginning at the splenic flexure, the calgb 80405 and Australasian Gastrointestinal Trials Group max trials excluded the transverse colon in their analysis. Furthermore, there is evidence to show that, even within rcc and lcc, significant heterogeneity is evident with respect to molecular characteristics 34,37 , such that classification by side could be oversimplifying a more complex interaction between tumour and treatment. Finally, to date, no data are available about the effect of ptl in the context of triplet therapy (that is, folfoxiri) combined with either bevacizumab or an efgr mAb.…”

Section: Limitationsmentioning

confidence: 99%

The Predictive Effect of Primary Tumour Location in the Treatment of Metastatic Colorectal Cancer: A Canadian Consensus Statement

et al. 2017

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In recently published data, the predictive value of primary tumour location for the treatment of metastatic colorectal cancer with available biologic therapies has been explored. Recognizing the potential effect of those data on clinical practice, we convened a meeting of Canadian experts who treat metastatic colorectal cancer to develop a set of national, evidence-based treatment guidelines based on primary tumour location. This report summarizes the relevant evidence and presents the consensus recommendations of those experts.

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Primary Tumor Site and Anti-EGFR Monoclonal Antibody Benefit in Metastatic Colorectal Cancer: A Meta-Analysis

Abstract: This meta-analysis demonstrated that LCC had markedly superior anti-EGFR mAb treatment benefit compared with RCC.

Cited by 9 publications

References 43 publications

EGFR Protein Expression in KRAS Wild-Type Metastatic Colorectal Cancer Is Another Negative Predictive Factor of the Cetuximab Therapy

EGFR Protein Expression in KRAS Wild-Type Metastatic Colorectal Cancer Is Another Negative Predictive Factor of the Cetuximab Therapy

Prognostic lncRNAs, miRNAs, and mRNAs Form a Competing Endogenous RNA Network in Colon Cancer

The Predictive Effect of Primary Tumour Location in the Treatment of Metastatic Colorectal Cancer: A Canadian Consensus Statement

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