{
  "abstract": "Background and Importance Sacituzumab govitecan is an antibody–drug conjugate indicated for metastatic breast cancer, whose active metabolite is SN-38. Like irinotecan, this metabolite is cleared by the UGT1A1 enzyme. Although genetic variants with level 1A evidence significantly affect enzymatic activity, systematic UGT1A1 genotyping prior to sacituzumab govitecan treatment is not currently implemented.Aim and Objectives To assess the clinical relevance of UGT1A1 variant genotyping in routine practice and analyse its potential impact in patients with breast cancer receiving sacituzumab govitecan.Material and Methods We conducted a retrospective study in two phases. First, a cohort of patients treated with irinotecan (2021–2023) was analysed to identify the prevalence of UGT1A1 variants (*6, *28, *37) compared with reference populations (1000 Genomes Project, gnomAD). Second, we examined a group of metastatic breast cancer patients treated with sacituzumab govitecan who developed severe toxicities (grade ≥3, CTCAE v5.0). Genotyping was performed using QuantStudio™ 12K-Flex (Applied Biosystems) and KlusterCaller software (LGC Genomics). Statistical analyses employed chi-square or Fisher’s exact test in R v4.3.2.Results We observed a statistically significant difference in the rs4148323 (UGT1A1 6) variant in the cohort of patients treated with irinotecan guided by UGT1A1 testing (n=120) compared with the global population (MAF=0 vs. Global MAF=0.034; p=0.0005). Moreover, 55% of irinotecan-treated patients carried UGT1A1 variants that required therapeutic recommendations. Among the breast cancer patients treated with sacituzumab govitecan who developed severe toxicities (n=12), four had the UGT1A128/28 genotype and two had UGT1A11/*28, classified as poor and intermediate metabolisers, respectively. Two of these patients required hospitalisation, one in intensive care and the other in the oncology ward.Conclusion and Relevance UGT1A1 genotyping prior to initiating sacituzumab govitecan treatment appears to be as important, if not more, for preventing severe adverse reactions as in patients treated with irinotecan. This strategy could help prevent serious toxicities, optimise clinical management, and improve therapeutic safety in these patients. Based on its prevalence, UGT1A1*6 genotyping is less relevant in our population compared with the global population.Conflict of Interest No conflict of interest",
  "authors": [
    {
      "affiliations": [
        "Hospital Universitario San Cecilio, Pharmacy, Granada, Spain"
      ],
      "name": "M Martinez"
    },
    {
      "affiliations": [
        "Husc, Pharmacy Hospital, Granada, Spain"
      ],
      "name": "MT Nieto-Sanchez"
    },
    {
      "affiliations": [
        "Husc, Pharmacy Hospital, Granada, Spain"
      ],
      "name": "MR Robles-Muñoz"
    },
    {
      "affiliations": [
        "Genyo, Genyo, Granada, Spain"
      ],
      "name": "A Torres-Garcia"
    },
    {
      "affiliations": [
        "Husc, Pharmacy Hospital, Granada, Spain"
      ],
      "name": "R Moron"
    },
    {
      "affiliations": [
        "Husc, Pharmacy Hospital, Granada, Spain"
      ],
      "name": "X Diaz-Villamarin"
    }
  ],
  "title": "5PSQ-021 Implementation of ugt1a1 genotyping prior to sacituzumab govitecan treatment: a need in real-world clinical practice",
  "uid": "62b29701-ea6a-5640-bb46-8adb29181d5e"
}