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- Title
EGFR Amplification in Metastatic Colorectal Cancer.
- Authors
Randon, Giovanni; Yaeger, Rona; Hechtman, Jaclyn F; Manca, Paolo; Fucà, Giovanni; Walch, Henry; Lee, Jeeyun; Élez, Elena; Seligmann, Jenny; Mussolin, Benedetta; Pagani, Filippo; Germani, Marco Maria; Ambrosini, Margherita; Rossini, Daniele; Ratti, Margherita; Salvà, Francesc; Richman, Susan D; Wood, Henry; Nanjangud, Gouri; Gloghini, Annunziata
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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).<bold>Conclusion: </bold>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.
- Subjects
COLORECTAL cancer; EPIDERMAL growth factor receptors; METASTASIS; OVERALL survival; BRAF genes; COLON tumors; RESEARCH; RESEARCH methodology; CELL receptors; EVALUATION research; COMPARATIVE studies; TRANSFERASES; RESEARCH funding; LONGITUDINAL method
- Publication
JNCI: Journal of the National Cancer Institute, 2021, Vol 113, Issue 11, p1561
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/djab069