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Effectiveness of first‐line cetuximab in wild‐type RAS metastatic colorectal cancer according to tumour BRAF mutation status from the EREBUS cohort
Author(s) -
Rouyer Magali,
François Eric,
Sa Cunha Antonio,
Monnereau Alain,
Big Emmanuelle,
Jové Jérémy,
Lassalle Régis,
DrozPerroteau Cécile,
Moore Nicholas,
Noize Pernelle,
FourrierRéglat Annie,
Smith Denis
Publication year - 2021
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.14472
Subject(s) - cetuximab , medicine , kras , colorectal cancer , oncology , cohort , panitumumab , progression free survival , cancer , proportional hazards model , multivariate analysis , overall survival
Aims Poor efficacy has been reported for patients with BRAF mutations for metastatic colorectal cancer (mCRC). Methods EREBUS is a French cohort study of wild‐type (wt) KRAS unresectable 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 additional RAS and BRAF mutation testing results. Progression‐free survival (PFS) and overall survival (OS) were assessed according to tumour mutation (mt) status: RAS mt/ BRAF any, RAS wt/ BRAF mt and RAS wt/ BRAF wt. 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: 64 RAS mt/ BRAF any (21%), 33 RAS wt/ BRAF mt (13%) and 213 RAS wt/ BRAF wt (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 with RAS mt/ BRAF any, 6.0 months [2.3–7.2] for patients with RAS wt/ BRAF mt, and 10.4 months [9.5–11.0] for patients with RAS wt/ BRAF wt. 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 for RAS wt/ BRAF mt vs RAS wt/ BRAF wt patients. Conclusions BRAF mutations were associated with markedly poorer outcomes in initially unresectable RAS wt mCRC patients treated by cetuximab in first‐line treatment.