Survival of patients with colorectal or pancreatic cancer who received <i>UGT1A1</i> genotype-guided dosing of irinotecan in the Netherlands (2017-2024): a retrospective, multicentre cohort study.
retrospective_cohort · Level III
Where this comes from
- Record sourced from PubMed, PMID 41777427.
- Also identified by DOI 10.1016/j.lanepe.2026.101629 and PMC identifier 12950460.
- Licence recorded as CC BY.
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Abstract
<i>UGT1A1</i> 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. 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. Patients were included in the primary analysis if irinotecan was dosed according to <i>UGT1A1</i> 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. 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: <i>P</i> = 0.54; OS: <i>P</i> = 0.42). In stratified Cox regression analyses, the adjusted hazard ratio of PMs <i>vs</i> IM/NMs was 1.02 (95% CI 0.78-1.32; <i>P</i> = 0.90) for PFS and 1.10 (95% CI 0.82-1.48; <i>P</i> = 0.51) for OS, indicating no significant differences exist in PFS or OS between 30% dose-reduced PMs and fully-dosed IM/NMs. Severe toxicity rates were comparable between 30% dose-reduced PMs and fully-dosed IM/NMs (<i>P</i> = 0.59). An upfront 30% dose reduction of irinotecan in UGT1A1 PMs does not lead to statistically significant differences in survival outcomes compared to fully-dosed IM/NMs. Therefore, <i>UGT1A1</i> genotype-guided dosing of irinotecan can be confidently performed to improve patient safety. No funding.