Survival of patients with colorectal or pancreatic cancer who received UGT1A1 genotype-guided dosing of irinotecan in the Netherlands (2017–2024): a retrospective, multicentre cohort study
Abstract
Summary Background UGT1A1 genotype-guided dosing reduces severe toxicity in UGT1A1 poor metaboliser (PM) patients treated with irinotecan. However, the impact of a dose reduction on survival remains unknown. 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. Methods We conducted a retrospective, multicentre cohort study in patients with pancreatic cancer or colorectal cancer treated with UGT1A1 genotype-guided irinotecan dosing at six Dutch hospitals between August 2017 and April 2024. Patients were included in the primary analysis if irinotecan was dosed according to UGT1A1 genotype (i.e. an initial 100% ± 10% dose intensity for IM/NMs and an initial 70% ± 10% dose intensity for PMs) in at least cycle 1. Survival analyses for PFS and OS were performed using Kaplan–Meier estimates and univariable and multivariable Cox regressions, stratified by tumour type. Safety was also assessed. Findings The primary analysis included 779 patients, 76 (9.8%) of whom were PMs. The median follow-up was 27.8 months (95% CI 15.2–31.6). No significant differences in PFS and OS rates were found between 30% dose-reduced PMs and fully-dosed IM/NMs (stratified log-rank test: PFS: P = 0.54; OS: P = 0.42). In stratified Cox regression analyses, the adjusted hazard ratio of PMs…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 779 participants or records.
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