Effectiveness of first-line cetuximab in wild-typeRASmetastatic colorectal cancer according to tumourBRAFmutation status from the EREBUS cohort

Aims Poor efficacy has been reported for patients withBRAFmutations for metastatic colorectal cancer (mCRC). Methods EREBUS is a French cohort study of wild-type (wt)KRASunresectable mCRC patients initiating a first-line treatment with cetuximab from 2009 to 2010, followed for two years (five years for vital status). Molecular genetics platforms have provided additionalRASandBRAFmutation testing results. Progression-free survival (PFS) and overall survival (OS) were assessed according to tumour mutation (mt) status:RASmt/BRAFany,RASwt/BRAFmt andRASwt/BRAFwt. Multivariate Cox analyses were used to evaluate association between mutation status and death or progression. Results A total of 389 patients were included in 65 centres and with a known tumour mutation status: 64RASmt/BRAFany (21%), 33RASwt/BRAFmt (13%) and 213RASwt/BRAFwt (87%). Respective baseline characteristics were: median age 65, 64 and 63 years, male gender 63%, 64% and 69%, Eastern Cooperative Oncology Group performance status <= 1 75%, 76% and 79%, and liver-only metastases 39%, 33% and 40%. Median progression-free survival was 8.0 months [5.9-9.3] for patients withRASmt/BRAFany, 6.0 months [2.3-7.2] for patients withRASwt/BRAFmt, and 10.4 months [9.5-11.0] for patients withRASwt/BRAFwt. Respectively, median overall survival was 18.4 months [10.9-23.3], 9.7 months [6.9-16.6] and 29.3 months [26.3-36.1]. In multivariate analyses, progression (HR = 2.71 [1.79-4.10]) and death (HR = 2.79 [1.81-4.30]) were more likely forRASwt/BRAFmtvs RASwt/BRAFwt patients. Conclusions BRAFmutations were associated with markedly poorer outcomes in initially unresectableRASwt mCRC patients treated by cetuximab in first-line treatment.