Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study

Moroni, Mauro; Veronese, Silvio; Benvenuti, Silvia; Marrapese, Giovanna; Sartore-Bianchi, Andrea; Nicolantonio, Federica Di; Gambacorta, Marcello; Siena, Salvatore; Bardelli, Alberto

doi:10.1016/s1470-2045(05)70102-9

Cited by 872 publications

(693 citation statements)

References 26 publications

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“…The articles were published between 2005 and 2011. Three studies 6,19,20 were conducted in France, 3 studies 13,18,21 were conducted in Italy, 1 study 14 was conducted in Switzerland, 1 study 17 was conducted in Figure 1. This is a flow chart of study selection for the current analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Individual data were extracted from 7 studies 6,13,14,[18][19][20][21] that included the available data for ORR but did not perform a comparison between 2 groups of patients.…”

Section: Data Extractionmentioning

confidence: 99%

“…12 Second, a few patients who have tumors with KRAS mutations occasionally respond to anti-EGFR treatment. 1,13,14 The tumors from those responsive patients predominantly harbored codon 13 mutations, and all codon 13 responders have p.G13D mutation. These findings indicate that the KRAS p.G13D mutation and KRAS codon 12 mutations may have a different effect on cetuximab efficacy.…”

Section: Introductionmentioning

confidence: 99%

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KRAS p.G13D mutation and codon 12 mutations are not created equal in predicting clinical outcomes of cetuximab in metastatic colorectal cancer

Chen

Huang

Yang

et al. 2012

Cancer

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BACKGROUND:The authors conducted a systematic review and meta-analysis to examine whether patients who had metastatic colorectal cancer (mCRC) with the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G13D mutation (an amino acid substitution at position 13 in KRAS from a glycine to an aspartic acid) and received cetuximab treatment had better clinical outcomes than patients who had mCRC tumors with KRAS codon 12 mutations. METHODS: Relevant studies were identified by a search of MEDLINE, EMBASE, the Chinese Biomedical Database, and Wan Fang Digital Journals from inception to October 2011. The primary clinical outcomes included the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The pooled relative risk (RR) or hazard ratio (HR) was estimated by using fixed-effects or random-effects models according to heterogeneity between studies. RESULTS: Ten studies were considered eligible that included 1487 patients with mCRC. Patients who had tumors with the KRAS p.G13D mutation had a significantly higher ORR (10 studies; RR, 1.642; 95% confidence interval [CI], 1.131-2.384), longer PFS (1 study; HR, 0.54; 95% CI, 0.36-0.81), and longer OS (1 study; HR, 0.52; 95% CI, 0.33-0.80) than patients who had tumors with KRAS codon 12 mutations. Compared with patients who had KRAS wild-type tumors, patients with the p.G13D mutation had a significantly lower ORR (9 studies; RR, 0.540; 95% CI, 0.381-0.765) and nonsignificantly shorter PFS (1 study; HR, 0.99; 95% CI, 0.68-1.45) and OS (1 study; HR, 1.01; 95% CI, 0.66-1.54). CONCLUSIONS: Patients who had mCRC with the KRAS p.G13D mutation appeared to benefit more from cetuximab than patients who had tumors with KRAS codon 12 mutations. However, because of the limited sample sizes in the current meta-analysis, these results should be interpreted with caution. Cancer 2013;119:714-21.

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Section: Methodsmentioning

confidence: 99%

“…Individual data were extracted from 7 studies 6,13,14,[18][19][20][21] that included the available data for ORR but did not perform a comparison between 2 groups of patients.…”

Section: Data Extractionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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KRAS p.G13D mutation and codon 12 mutations are not created equal in predicting clinical outcomes of cetuximab in metastatic colorectal cancer

Chen

Huang

Yang

et al. 2012

Cancer

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“…There are several methods for detecting and determining EGFR gene copy number, or dosage, including FISH, 25,30,102 chromogenic in situ hybridization, 32,103 and realtime quantitative PCR. 10,104,105 When compared with EGFR mutations, EGFR gene copy number gain was a less sensitive and less specific marker, and may therefore not be considered clinically suitable for patient selection. 31 …”

Section: Egfr Copy Number Alterationmentioning

confidence: 99%

Molecular pathology of lung cancer: key to personalized medicine

et al. 2012

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The majority of lung adenocarcinoma patients with epidermal growth factor receptor-(EGFR) mutated or EML4-ALK rearrangement-positive tumors are sensitive to tyrosine kinase inhibitors. Both primary and acquired resistance in a significant number of those patients to these therapies remains a major clinical problem. The specific molecular mechanisms associated with tyrosine kinase inhibitor resistance are not fully understood. Clinicopathological observations suggest that molecular alterations involving so-called 'driver mutations' could be used as markers that aid in the selection of patients most likely to benefit from targeted therapies. In this review, we summarize recent developments involving the specific molecular mechanisms and markers that have been associated with primary and acquired resistance to EGFR-targeted therapy in lung adenocarcinomas. Understanding these mechanisms may provide new treatment avenues and improve current treatment algorithms.

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“…3,6,12,15,22,23,[30][31][32][33] In both the lung and the colon, some authors have reported a correlation with the presence of increased EGFR copy number and response to EGFR tyrosine kinase inhibitors and anti-EGFR monoclonal antibodies, respectively. Others have found conflicting results and, therefore, current recommendations for lung adenocarcinoma favor mutational testing over EGFR polysomy.…”

Section: Discussionmentioning

confidence: 99%

EGFR alterations and EML4-ALK rearrangement in primary adenocarcinoma of the urinary bladder

et al. 2014

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The identification of mutations in epidermal growth factor receptor (EGFR) and translocations involving anaplastic lymphoma kinase (ALK) in lung adenocarcinoma has drastically changed understanding of the disease and led to the development of targeted therapies. Adenocarcinoma of the urinary bladder is rare and poorly understood at the molecular level. We undertook this study to determine whether EGFR mutations, increases in EGFR copy number, or ALK translocations are present in these tumors. Twenty-eight cases of primary bladder adenocarcinoma were analyzed. For EGFR mutational analysis, PCR-amplified products were analyzed on the Q24 Pyrosequencer with Qiagen EGFR Pyro Kits. All cases were analyzed via fluorescence in situ hybridization (FISH) using Vysis ALK Break Apart FISH Probes for detection of ALK chromosomal translocation and Vysis Dual Color Probes to assess for increased gene copy number of EGFR. None of the 28 cases examined showed mutational events in EGFR or ALK rearrangements. EGFR polysomy was seen in 10 out of 28 (36%) cases. No correlation with EGFR polysomy was seen in the tumors with respect to age, histologic subtypes, pathologic stage, or lymph node metastasis. In summary, EGFR mutations and ALK rearrangements do not appear to be involved in the development of primary adenocarcinoma of the urinary bladder. A subgroup of cases (36%), however, demonstrated increased gene copy number of EGFR by FISH.

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Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study

Cited by 872 publications

References 26 publications

KRAS p.G13D mutation and codon 12 mutations are not created equal in predicting clinical outcomes of cetuximab in metastatic colorectal cancer

KRAS p.G13D mutation and codon 12 mutations are not created equal in predicting clinical outcomes of cetuximab in metastatic colorectal cancer

Molecular pathology of lung cancer: key to personalized medicine

EGFR alterations and EML4-ALK rearrangement in primary adenocarcinoma of the urinary bladder

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