Anti-EGFR Agents in Patients With Right-sided Advanced Colorectal Cancer With Wild-type RAS and AREG/EREG High Status

Inclusion Criteria for Registration: * Age ≥18 years * Biopsy-confirmed adenocarcinoma of the colon with a right primary tumour location * aCRC defined as either M1 or locally inoperable disease * Tumour RAS status either wild-type (by local testing) or unknown * Fit for combination chemotherapy plus anti-EGFR agent * Sufficient tumour material for EREG/AREG analysis * Written informed consent for registration Exclusion Criteria for Registration * Tumour RAS-mutation present * Prior chemotherapy for aCRC * Prior anti-EGFR agent therapy Inclusion Criteria for Randomisation: * Registered in ARIEL-ENGIC * Local testing confirms tumour RAS-wt status * ARIEL-ENGIC central testing confirms tumour EREG/AREG high * Tumour measurable by RECIST v1.1 criteria on CT scan * Participants have had CT scan within the timeframes stipulated (If there is a contrast reaction, then non-contrast CT with MRI is acceptable, assuming at least one of these modalities shows measurable disease at baseline for ETS evaluation and both modalities are repeated at the trial timepoints at week 8 and 16 and every 8 weeks until disease progression.) * Pre-randomisation laboratory tests : * Neutrophils ≥1.5 x109/l and platelet count ≥100 x109/l * Serum bilirubin ≤ 1.25 x upper limit of normal (ULN), alkaline phosphatase * 5x ULN, and serum transaminase (either AST or ALT) ≤ 2.5 x ULN * Estimated creatinine clearance ≥50ml/min (creatinine clearance estimated as per local practice) * WHO performance status…