This study evaluated whether upfront 30% dose reductions of irinotecan in UGT1A1 PMs affect survival by comparing progression-free survival (PFS) and overall survival (OS) between 30% dose-reduced PMs and fully-dosed UGT1A1 intermediate and normal metaboliser (IM/NM) patients.<h4>Methods</h4>We conducted a retrospective, multicentre cohort study in patients with pancreatic cancer or colorectal cancer treated with <i>UGT1A1</i> genotype-guided irinotecan dosing at six Dutch hospitals between August 2017 and April 2024. This evidence concerns the gene UGT1A1 and colorectal cancer.