{
  "abstract": "Background and Importance UGT1A1 genotype-guided dosing significantly reduces the incidence of severe toxicity in UGT1A1 poor metabolizer (PM) patients treated with irinotecan (Hulshof et al. Eur J Cancer 2022). However, the impact of UGT1A1 genotype-guided irinotecan dosing on survival outcomes remains unknown.Aim and Objectives This study evaluated whether upfront 30% dose reductions of irinotecan in UGT1A1 PMs affect survival by comparing progression-free (PFS) and overall survival (OS) between PMs treated with an initial 30% dose-reduction and fully dosed intermediate and normal metabolizers (IM/NMs).Materials and Methods We conducted a retrospective, multicentre cohort study in patients with pancreatic cancer (PC) or colorectal cancer (CRC) treated with UGT1A1 genotype-guided irinotecan dosing at six Dutch hospitals between Aug 2017–Apr 2024. Patients were included in the primary analysis if irinotecan was dosed according to UGT1A1 genotype (i.e. 100%±10% dose intensity for IM/NMs and 70%±10% for PMs) in at least cycle 1. Survival analyses were performed using Kaplan-Meier estimates and multivariable Cox regressions, stratified by tumor type. Safety was also assessed.Results In total, 779 patients were included in the primary analysis, 76 (9.8%) of whom were PMs. PFS and OS rates were comparable over time between PMs and IM/NMs (stratified log-rank test: PFS: P = 0.542; OS: P = 0.419) (figure 1). For patients with PC, median PFS was 9.0 months (95%CI: 6.2-11.8) in PMs and 8.3 months (95%CI: 7.2-9.4) in IM/NMs. For patients with CRC, median PFS was 6.2 months (95%CI: 5.1-7.3) in PMs and 6.0 months (95%CI: 5.3-6.7) in IM/NMs. Median OS was not statistically significant between PMs and IM/NMs. The adjusted hazard ratio of PMs vs IM/NMs was 1.015 (95%CI: 0.78-1.32; P = 0.90) for PFS and was 1.10 (95%CI: 0.82-1.48; P = 0.51) for OS, indicating no significant differences in survival outcomes between 30% dose-reduced PMs and fully dosed IM/NMs. Severe toxicity rates were comparable between PMs and IM/NMs.Abstract NP-012 Figure 1Carbon footprint savings achieved by delivering outpatient medications to community pharmaciesConclusion and Relevance Survival of UGT1A1 poor metabolizers is not affected by an upfront 30% dose reduction of irinotecan. Therefore, UGT1A1 genotype-guided dosing of irinotecan can be confidently performed and should become the new standard-of-care dosing strategy for irinotecan to improve patient safety.",
  "authors": [
    {
      "affiliations": [
        "Department of Clinical Pharmacy, Catharina Hospital, Eindhoven",
        "Department of Clinical Pharmacy and Toxicology, Leiden University Medical Centre, Leiden"
      ],
      "name": "Sofía LJ Peeters"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam",
        "Department of Clinical Chemistry, Erasmus University Medical Centre, Rotterdam"
      ],
      "name": "Niels Heersche"
    },
    {
      "affiliations": [
        "Department of Clinical Pharmacy, Catharina Hospital, Eindhoven",
        "Department of Clinical Pharmacy and Toxicology, Leiden University Medical Centre, Leiden"
      ],
      "name": "Doortje MM Bohm"
    },
    {
      "affiliations": [
        "Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden"
      ],
      "name": "Stefan Böhringer"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam"
      ],
      "name": "Roselien Guiljam"
    },
    {
      "affiliations": [
        "Department of Clinical Pharmacy, Catharina Hospital, Eindhoven"
      ],
      "name": "Marije Joosse"
    },
    {
      "affiliations": [
        "Department of Clinical Pharmacy, Catharina Hospital, Eindhoven"
      ],
      "name": "Aisha Osman"
    },
    {
      "affiliations": [
        "Department of Clinical Pharmacy, Catharina Hospital, Eindhoven",
        "Department of Clinical Pharmacy and Toxicology, Leiden University Medical Centre, Leiden"
      ],
      "name": "Emma C Hulshof"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam"
      ],
      "name": "Femke M de Man"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam",
        "Department of Clinical Chemistry, Erasmus University Medical Centre, Rotterdam"
      ],
      "name": "Mirjam de With"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Catharina Hospital, Eindhoven"
      ],
      "name": "Irene EG van Hellemond"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Maasstad Hospital, Rotterdam"
      ],
      "name": "Brigitte CM Haberkorn"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Reinier de Graaf Gasthuis Hospital, Delft"
      ],
      "name": "Arjan J Verschoor"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Jeroen Bosch Hospital, ‘s Hertogenbosch"
      ],
      "name": "Miriam L Wumkes"
    },
    {
      "affiliations": [
        "Department of Clinical Chemistry, Erasmus University Medical Centre, Rotterdam"
      ],
      "name": "Ron HN van Schaik"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Catharina Hospital, Eindhoven"
      ],
      "name": "Anna MJ Thijs"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Leiden University Medical Centre, Leiden"
      ],
      "name": "Hans Gelderblom"
    },
    {
      "affiliations": [
        "Department of Clinical Pharmacy and Toxicology, Leiden University Medical Centre, Leiden"
      ],
      "name": "Henk-Jan Guchelaar"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam"
      ],
      "name": "Ron HJ Mathijssen"
    },
    {
      "affiliations": [
        "Department of Clinical Pharmacy, Catharina Hospital, Eindhoven",
        "Department of Clinical Pharmacy and Toxicology, Leiden University Medical Centre, Leiden"
      ],
      "name": "Maarten J Deenen"
    }
  ],
  "title": "NP-012 Survival of patients with colorectal or pancreatic cancer who received UGT1A1 genotype-guided dosing of irinotecan: a multicentre real-world study",
  "uid": "18c28dbe-ef5a-5efd-9f6d-9375080028ca"
}