Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, the Netherlands.
Department of Clinical Chemistry, Inselspital, Bern University Hospital & University of Bern, INO F, Bern, Switzerland.
ESMO Open. 2023 Apr;8(2):101197. doi: 10.1016/j.esmoop.2023.101197. Epub 2023 Mar 28.
The main cause for fluoropyrimidine-related toxicity is deficiency of the metabolizing enzyme dihydropyrimidine dehydrogenase (DPD). In 2020, the European Medicines Agency (EMA) recommended two methods for pre-treatment DPD deficiency testing in clinical practice: phenotyping using endogenous uracil concentration or genotyping for DPYD risk variant alleles. This study assessed the DPD testing implementation status in Europe before (2019) and after (2021) the release of the EMA recommendations.
The survey was conducted from 16 March 2022 to 31 July 2022. An electronic form with seven closed and three open questions was e-mailed to 251 professionals with DPD testing expertise of 34 European countries. A descriptive analysis was conducted.
We received 79 responses (31%) from 23 countries. Following publication of the EMA recommendations, 87% and 75% of the countries reported an increase in the amount of genotype and phenotype testing, respectively. Implementation of novel local guidelines was reported by 21 responders (27%). Countries reporting reimbursement of both tests increased in 2021, and only four (18%) countries reported no coverage for any testing type. In 2019, major implementation drivers were 'retrospective assessment of fluoropyrimidine-related toxicity' (39%), and in 2021, testing was driven by 'publication of guidelines' (40%). Although the major hurdles remained the same after EMA recommendations-'lack of reimbursement' (26%; 2019 versus 15%; 2021) and 'lack of recognizing the clinical relevance by medical oncologists' (25%; 2019 versus 8%; 2021)-the percentage of specialists citing these decreased. Following EMA recommendations, 25% of responders reported no hurdles at all in the adoption of the new testing practice in the clinics.
The EMA recommendations have supported the implementation of DPD deficiency testing in Europe. Key factors for successful implementation were test reimbursement and clear clinical guidelines. Further efforts to improve the oncologists' awareness of the clinical relevance of DPD testing in clinical practice are needed.
氟嘧啶类药物相关毒性的主要原因是代谢酶二氢嘧啶脱氢酶（DPD）缺乏。2020 年，欧洲药品管理局（EMA）建议在临床实践中使用两种方法进行预处理 DPD 缺乏症检测：使用内源性尿嘧啶浓度进行表型检测或针对 DPYD 风险变异等位基因进行基因分型。本研究评估了 EMA 建议发布前后（2019 年和 2021 年）欧洲的 DPD 检测实施情况。
该调查于 2022 年 3 月 16 日至 7 月 31 日进行。我们向 34 个欧洲国家的 251 名具有 DPD 检测专业知识的专业人员发送了一份包含七个封闭式和三个开放式问题的电子表格。进行了描述性分析。
我们从 23 个国家收到了 79 份（31%）回复。EMA 建议发布后，分别有 87%和 75%的国家报告称基因分型和表型检测数量增加。21 名答复者报告实施了新的地方指南。2021 年，报告同时报销两种检测的国家有所增加，只有 4 个（18%）国家报告没有涵盖任何检测类型。2019 年，主要实施驱动因素是“氟嘧啶相关毒性的回顾性评估”（39%），而 2021 年，测试是由“指南的发布”（40%）驱动的。尽管 EMA 建议发布后仍然存在同样的主要障碍——“缺乏报销”（26%；2019 年与 15%；2021 年）和“医学肿瘤学家未能认识到临床相关性”（25%；2019 年与 8%；2021 年）——但引用这些障碍的专家比例有所下降。EMA 建议发布后，25%的应答者报告称在临床实践中采用新的检测实践时没有任何障碍。
EMA 建议支持了欧洲 DPD 缺乏症检测的实施。成功实施的关键因素是检测报销和明确的临床指南。需要进一步努力提高肿瘤学家对 DPD 检测在临床实践中的临床相关性的认识。
