e15547 Background: Poor efficacy of cetuximab has been reported in patients with RAS/BRAF mt. There are few data about cetuximab benefit in real-life according to RAS/BRAF mt status. Methods: EREBUS is a multicenter (n = 65) cohort of KRAS wild-type (wt) unresectable mCRC patients initiating 1st-line cetuximab from 2009 to 2010, followed for 2 years (5 years for vital status). Objective response rate (ORR), metastases resection rate, progression-free survival (PFS) and overall survival (OS) were evaluated according to mt status: RASmt (whatever BRAF status), RASwt/BRAFmt and RASwt/BRAFwt (i.e. 2xWT). Multivariate Cox analyses were used to evaluate the association between mt status and death or progression. Results: 389 patients were included; RAS/BRAF status was known for 310 (80%): 64 RASmt (21%), 33 RASwt/BRAFmt (11%) and 213 2xWT (69%). Respective baseline characteristics were: median age 65, 64 and 63 years, male gender 63%, 64% and 69%, ECOG-PS 0-1 75%, 76% and 79%, liver only metastases 39%, 33% and 40%. ORR was 40.6% 95%CI [28.5-53.6] in RASmt patients, 30.3% [15.6-48.7] in RASwt/BRAFmt patients and 62.4% [55.8-69.0] in 2xWT patients. Metastases resection was performed in 12 RASmt patients (18.8% [10.1-30.5]; 8 radical resections R0/R1/radiofrequency), 2 RASwt/BRAFmt patients (6.1% [0.7-20.2]; 2 radical resections) and 75 2xWT patients (35.2% [28.8-41.6]; 47 radical resections). Median PFS (months) was 8.0 [5.9-9.3] in RASmt patients, 6.0 [2.3-7.2] in RASwt/BRAFmt patients and 10.4 [9.5-11.0] in 2xWT patients. Median OS (months) was 18.4 [10.9-23.3] in RASmt patients, 9.7 [6.9-16.6] in RASwt/BRAFmt patients and 29.3 [26.3-36.1] in 2xWT patients. In multivariate analyses, death (HR 3.13 [2.04-4.79]) and progression (HR 2.69 [1.78-4.07]) were more likely for RASwt/BRAFmt patients vs. 2xWT patients. In reference to 2xWT patients, HR for death was 1.63 [1.13-2.35] for RASmt/BRAFwt patients and HR for progression 1.41 [0.98-2.04] (p = 0.06). Conclusions: EREBUS confirms in real-life the difference in clinical outcomes with tumoral RAS/BRAF mutation in unresectable mCRC treated by 1st-line cetuximab, showing the greatest effectiveness in 2xWT patients.