EGFR Amplification in Metastatic Colorectal Cancer
Menée à partir de données cliniques portant sur 1 521 patients atteints d'un cancer colorectal métastatique, cette étude identifie les caractéristiques cliniques et moléculaires des tumeurs présentant une amplification du gène du récepteur EGFR
Résumé en anglais
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 (mAbs). Herein, we aimed to characterize the clinical and molecular landscape of EGFR-amplified metastatic colorectal cancer (mCRC).
Methods : In this multinational cohort study, we compared clinical data of 62 patients with EGFR-amplified vs. 1459 EGFR non-amplified mCRC, as well as comprehensive genomic data of 35 EGFR-amplified vs. 439 EGFR non-amplified RAS/BRAF wild-type and microsatellite stable (MSS) tumor samples.
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 non-amplified. Overall, EGFR-amplified samples had higher median fraction of genome altered compared to EGFR non-amplified, 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-NA) vs. EGFR non-amplified ones (24.0 months; 95% CI = 22.8-25.6; hazard ratio [HR] = 0.30, 95% CI = 0.20-0.44, P<.001; adjusted HR = 0.46, 95%CI = 0.30-0.69, 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-NA] vs. 29.1 months [95% CI = 27.0-31.9], respectively; HR = 0.46, 95%CI = 0.28-0.76, 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.
