Cetuximab Shows Activity in Colorectal Cancer Patients With Tumors for Which FISH Analysis Does Not Detect an Increase in EGFR Gene Copy Number

Italiano, Antoîne; Follana, Philippe; Caroli, François-Xavier; Badetti, Jean-Luc; Benchimol, Daniel; Garnier, G.; Gugenheim, Jean; Haudebourg, Juliette; Keslair, Frédérique; Lesbats, G; Lledo, Gérard; Roussel, Jean‐François; Pédeutour, Florence; François, Ετιεννε

doi:10.1245/s10434-007-9667-2

Cited by 85 publications

(58 citation statements)

References 29 publications

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“…More recently, increased EGFR gene copy number as detected by fluorescence in situ hybridization (FISH) was associated with response to cetuximab or panitumumab [33]. This has been contradicted by findings that FISH analysis of EGFR amplification does not select all colorectal cancer patients who may benefit from cetuximab therapy [34]. These discrepancies could be explained by tumor heterogeneity, presence of heterogeneous EGFR populations with different levels of low-and high-affinity sites, lack of standardized EGFR testing methods, and poor correlation between EGFR protein and DNA levels [17,35].…”

Section: Egfr and Colorectal Cancermentioning

confidence: 99%

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program

et al. 2008

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Novel therapeutic agents targeting the epidermal growth factor receptor (EGFR) have improved outcomes for patients with colorectal carcinoma. However, these therapies are effective only in a subset of patients. Activating mutations in the KRAS gene are found in 30-40% of colorectal tumors and are associated with poor response to anti-EGFR therapies. Thus, KRAS mutation status can predict which patient may or may not benefit from anti-EGFR therapy. Although many diagnostic tools have been developed for KRAS mutation analysis, validated methods and standardized testing procedures are lacking. This poses a challenge for the optimal use of anti-EGFR therapies in the management of colorectal carcinoma. Here we review the molecular basis of EGFR-targeted therapies and the resistance to treatment conferred by KRAS mutations. We also present guideline recommendations and a proposal for a European quality assurance program to help ensure accuracy and proficiency in KRAS mutation testing across the European Union.

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Section: Egfr and Colorectal Cancermentioning

confidence: 99%

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program

et al. 2008

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“…However, tumour response was observed in colorectal tumours without an increase of EGFR copy number (Italiano et al, 2008) and discrepant results were observed when EGFR copy number was assessed by quantitative PCR and not by FISH (Vallbohmer et al, 2005;Lenz et al, 2006;Khambata-Ford et al, 2007).…”

Section: Pik3ca Mutations and Loss Of Pten Expressionmentioning

confidence: 96%

Oncogenic mutations as predictive factors in colorectal cancer

2010

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“…Indeed, BRAF V600E mutation seems to be a marker of poor prognosis (9,10,14,15). Furthermore, studies that examined PIK3CA mutations, loss of PTEN expression, EGFR gene copy number, and polymorphisms of fragment c g receptors have reported conflicting results (14,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)). Finally, mRNA expression level of amphiregulin and epiregulin seems to be of limited clinical interest because of the inability to set an appropriate threshold limit (28,29).…”

Section: Introductionmentioning

confidence: 99%

Hsa-miR-31-3p Expression Is Linked to Progression-free Survival in Patients with KRAS Wild-type Metastatic Colorectal Cancer Treated with Anti-EGFR Therapy

Manceau

Imbeaud

Thiébaut

et al. 2014

Clinical Cancer Research

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Purpose: To identify microRNAs (miRNA) that predict response to anti-EGFR antibodies in patients with wild-type KRAS metastatic colorectal cancer (mCRC).Experimental Design: miRNA profiling was performed in a training set of 87 patients with mCRC refractory to chemotherapy treated with anti-EGFR antibodies. This included 33 fresh-frozen (FF) and 35 formalin-fixed paraffin-embedded (FFPE) samples retrospectively collected and 19 prospectively collected FF samples. An independent validation cohort consisting of 19 FF and 26 FFPE prospectively collected samples from patients with mCRC treated with anti-EGFR antibodies was used to confirm our findings.Results: After screening the expression of 1,145 miRNAs in FF samples from the training set, we identified that hsa-miR-31-3p expression level was significantly associated with progression-free survival (PFS). Statistical models based on miRNA expression discriminated between high and low risk of progression for both FF and FFPE samples. These models were confirmed in the validation cohort for both FF [HR, 4.1; 95% confidence interval (CI), 1.1-15.3; P < 0.04] and FFPE samples (HR, 2.44; 95% CI, 1.1-5.4; P ¼ 0.028). The percentage of variation of RECIST criteria in the validation series was significantly associated with the expression level of hsa-miR-31-3p (r 2 ¼ 0.49; P ¼ 0.0035) and risk status determined by hsa-miR-31-3p expression level (P ¼ 0.02, Kruskal-Wallis rank test). Nomograms were built and validated to predict PFSdepending on hsa-miR-31-3p expression level. Following in vitro studies, we identified 47 genes regulated by hsa-miR-31-3p. Conclusion: Hsa-miR-31-3p seems to be a new mCRC biomarker whose expression level allows for the identification of patients with wild-type KRAS mCRC who are more likely to respond to anti-EGFR therapy.

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Cetuximab Shows Activity in Colorectal Cancer Patients With Tumors for Which FISH Analysis Does Not Detect an Increase in EGFR Gene Copy Number

Abstract: EGFR FISH analysis does not seem to be a sufficiently robust test for selecting candidate CRC patients for cetuximab therapy.

Cited by 85 publications

References 29 publications

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program

Oncogenic mutations as predictive factors in colorectal cancer

Hsa-miR-31-3p Expression Is Linked to Progression-free Survival in Patients with KRAS Wild-type Metastatic Colorectal Cancer Treated with Anti-EGFR Therapy

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