{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Randon G"],"funding":["AIRC-CRUK-FC AECC Accelerator","AIRC","NCI NIH HHS","National Institutes of Health","FONDAZIONE AIRC under 5 per Mille 2018"],"pagination":["1561-1569"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8562951"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["113(11)"],"pubmed_abstract":["<h4>Background</h4>EGFR amplification occurs in about 1% of metastatic colorectal cancers (mCRCs) but is not routinely tested as a prognostic or predictive biomarker for patients treated with anti-EGFR monoclonal antibodies. Herein, we aimed to characterize the clinical and molecular landscape of EGFR-amplified mCRC.<h4>Methods</h4>In this multinational cohort study, we compared clinical data of 62 patients with EGFR-amplified vs 1459 EGFR nonamplified mCRC, as well as comprehensive genomic data of 35 EGFR-amplified vs 439 EGFR nonamplified RAS/BRAF wild-type and microsatellite stable (MSS) tumor samples. All statistical tests were 2-sided.<h4>Results</h4>EGFR amplification was statistically significantly associated with left primary tumor sidedness and RAS/BRAF wild-type status. All EGFR-amplified tumors were MSS and HER2 nonamplified. Overall, EGFR-amplified samples had higher median fraction of genome altered compared with EGFR-nonamplified, RAS/BRAF wild-type MSS cohort. Patients with EGFR-amplified tumors reported longer overall survival (OS) (median OS = 71.3 months, 95% confidence interval [CI] = 50.7 to not available [NA]) vs EGFR-nonamplified ones (24.0 months; 95% CI = 22.8 to 25.6; hazard ratio [HR] = 0.30, 95% CI = 0.20 to 0.44; P < .001; adjusted HR = 0.46, 95% CI = 0.30 to 0.69; P < .001). In the subgroup of patients with RAS/BRAF wild-type mCRC exposed to anti-EGFR-based therapy, EGFR amplification was again associated with better OS (median OS = 54.0 months, 95% CI = 35.2 to NA, vs 29.1 months, 95% CI = 27.0 to 31.9, respectively; HR = 0.46, 95% CI = 0.28 to 0.76; P = .002).<h4>Conclusion</h4>Patients with EGFR-amplified mCRC represent a biologically defined subgroup and merit dedicated clinical trials with novel and more potent EGFR-targeting strategies beyond single-agent monoclonal antibodies."],"journal":["Journal of the National Cancer Institute"],"pubmed_title":["EGFR Amplification in Metastatic Colorectal Cancer."],"pmcid":["PMC8562951"],"funding_grant_id":["IG 2018 - ID. 21923","R01 CA233736","P30 CA008748","ID. 21091","IG 2019 - ID. 23624","22795 (AB)"],"pubmed_authors":["Elez E","de Braud F","Bardelli A","Lee J","Manca P","Ambrosini M","Pietrantonio F","Randon G","Gloghini A","Yaeger R","Seligmann J","Rossini D","Salva F","Nanjangud G","Pagani F","Fuca G","Walch H","Hechtman JF","Richman SD","Wood H","Mussolin B","Germani MM","Milione M","Morano F","Ratti M","Cremolini C"],"additional_accession":[]},"is_claimable":false,"name":"EGFR Amplification in Metastatic Colorectal Cancer.","description":"<h4>Background</h4>EGFR amplification occurs in about 1% of metastatic colorectal cancers (mCRCs) but is not routinely tested as a prognostic or predictive biomarker for patients treated with anti-EGFR monoclonal antibodies. Herein, we aimed to characterize the clinical and molecular landscape of EGFR-amplified mCRC.<h4>Methods</h4>In this multinational cohort study, we compared clinical data of 62 patients with EGFR-amplified vs 1459 EGFR nonamplified mCRC, as well as comprehensive genomic data of 35 EGFR-amplified vs 439 EGFR nonamplified RAS/BRAF wild-type and microsatellite stable (MSS) tumor samples. All statistical tests were 2-sided.<h4>Results</h4>EGFR amplification was statistically significantly associated with left primary tumor sidedness and RAS/BRAF wild-type status. All EGFR-amplified tumors were MSS and HER2 nonamplified. Overall, EGFR-amplified samples had higher median fraction of genome altered compared with EGFR-nonamplified, RAS/BRAF wild-type MSS cohort. Patients with EGFR-amplified tumors reported longer overall survival (OS) (median OS = 71.3 months, 95% confidence interval [CI] = 50.7 to not available [NA]) vs EGFR-nonamplified ones (24.0 months; 95% CI = 22.8 to 25.6; hazard ratio [HR] = 0.30, 95% CI = 0.20 to 0.44; P < .001; adjusted HR = 0.46, 95% CI = 0.30 to 0.69; P < .001). In the subgroup of patients with RAS/BRAF wild-type mCRC exposed to anti-EGFR-based therapy, EGFR amplification was again associated with better OS (median OS = 54.0 months, 95% CI = 35.2 to NA, vs 29.1 months, 95% CI = 27.0 to 31.9, respectively; HR = 0.46, 95% CI = 0.28 to 0.76; P = .002).<h4>Conclusion</h4>Patients with EGFR-amplified mCRC represent a biologically defined subgroup and merit dedicated clinical trials with novel and more potent EGFR-targeting strategies beyond single-agent monoclonal antibodies.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Nov","modification":"2025-04-04T19:57:41.843Z","creation":"2025-04-04T19:57:41.843Z"},"accession":"S-EPMC8562951","cross_references":{"pubmed":["33825902"],"doi":["10.1093/jnci/djab069"]}}