EGFR amplification in metastatic colorectal cancer Journal Article
| Authors: | Randon, G.; Yaeger, R.; Hechtman, J. F.; Manca, P.; Fucà, G.; Walch, H.; Lee, J.; Élez, E.; Seligmann, J.; Mussolin, B.; Pagani, F.; Germani, M. M.; Ambrosini, M.; Rossini, D.; Ratti, M.; Salvà, F.; Richman, S. D.; Wood, H.; Nanjangud, G.; Gloghini, A.; Milione, M.; Bardelli, A.; de Braud, F.; Morano, F.; Cremolini, C.; Pietrantonio, F. |
| Article Title: | EGFR amplification in metastatic colorectal cancer |
| Abstract: | Background: 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. Methods: 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. Results: 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). Conclusion: 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. |
| Keywords: | cetuximab; panitumumab; dna; sensitivity; wild-type; predictive biomarker; genomic landscape; amphiregulin expression |
| Journal Title: | JNCI: Journal of the National Cancer Institute |
| Volume: | 113 |
| Issue: | 11 |
| ISSN: | 0027-8874 |
| Publisher: | Oxford University Press |
| Date Published: | 2021-11-01 |
| Start Page: | 1561 |
| End Page: | 1569 |
| Language: | English |
| ACCESSION: | WOS:000744517000019 |
| DOI: | 10.1093/jnci/djab069 |
| PROVIDER: | wos |
| PMCID: | PMC8562951 |
| PUBMED: | 33825902 |
| Notes: | Article -- Source: Wos |
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