Retrospective cohort study of survival or colorectal or pancreatic cancer patients receiving UGT1A1 genotype-guided irinotecan dosing

UGT1A1 genotype-guided dosing reduces severe toxicity in UGT1A1 poor metabolizer (PM) patients treated with irinotecan. However, the impact of dose reduction on survival is unknown. A retrospective cohort study at six centers in The Netherlands evaluated whether upfront 30% dose reduction 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 metabolizer (IM/NM) patients with colorectal or pancreatic cancer. 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 or OS rates were found between the dose-reduced PMs and fully-dosed IM/NMs (PFS: p=0.54; OS: p=0.42). Severe toxicity rates were comparable between the two groups. The authors conclude that UGT1A1 genotype-guided dosing of irinotecan can be safely performed to improve patient safety.