Scailteux Lucie-Marie, Bezin Julien, Gundelwein Marion, Edeline Julien, Oger Emmanuel, Balusson Frédéric, Pariente Antoine
Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Rennes, France.
Pharmacovigilance, Pharmacoepidemiology and Drug Information Centre, Rennes University Hospital, Rennes, France.
Fundam Clin Pharmacol. 2025 Apr;39(2):e70004. doi: 10.1111/fcp.70004.
(Pre-)clinical studies have not ruled out a potential risk of second primary cancer (SCP) under the effect of some new androgen receptor pathway inhibitors (ARPIs), especially enzalutamide (ENZ).
Using the French health reimbursement claims database (Système National des Données de Santé), we designed a case-control study nested in a 2013-2020 cohort of new users of androgen-deprivation therapy. The cases were patients with a first diagnosis of SPC, identified beyond 12 months following cohort entry and up to December 31st 2021; up to 10 controls were matched per case, based on age and cohort entry date. The main analysis focused on patients who had not switched to a different ARPI. Applying a one-year lag time, we determined the most frequent and longest cumulative exposure patterns to abiraterone (ABI) or ENZ and estimated the odds ratios.
The cohort comprised 147 092 patients, including 7928 cases and 78 554 controls eligible for analysis. The SPCs mainly involve the digestive organs, the urinary tract, or the lungs. Recent and short exposure to ENZ was associated with SPC: OR 1.7, 95% CI [1.2-2.4]. Recent one full year of exposure to ABI, as well as full-year plus part of the second year, was associated with SPC: OR 1.8 [1.2-2.7] and 2.3 [1.3-4.0], respectively.
DISCUSSION/CONCLUSION: SPC cases were mainly observed among recently exposed patients, which could be linked to a detection bias. The insufficient number of patients exposed over many years means that no definitive conclusions can be drawn.
（临床前）研究尚未排除某些新型雄激素受体通路抑制剂（ARPI），尤其是恩杂鲁胺（ENZ）作用下发生第二原发性癌症（SCP）的潜在风险。
利用法国医保报销索赔数据库（全国健康数据系统），我们设计了一项巢式病例对照研究，该研究纳入了2013年至2020年接受雄激素剥夺治疗的新用户队列。病例为首次诊断为SPC的患者，在队列入组后12个月后至2021年12月31日期间确诊；每例病例最多匹配10名对照，匹配因素为年龄和队列入组日期。主要分析集中在未改用其他ARPI的患者。采用一年的滞后时间，我们确定了阿比特龙（ABI）或ENZ最常见和最长的累积暴露模式，并估计了比值比。
该队列包括147092名患者，其中7928例病例和78554名对照符合分析条件。SPC主要累及消化器官、泌尿系统或肺部。近期和短期接触ENZ与SPC相关：比值比为1.7，95%置信区间[1.2 - 2.4]。近期连续一整年接触ABI以及连续一整年加第二年部分时间接触ABI均与SPC相关：比值比分别为1.8[1.2 - 2.7]和2.3[1.3 - 4.0]。
讨论/结论：SPC病例主要在近期暴露的患者中观察到，这可能与检测偏倚有关。多年暴露患者数量不足意味着无法得出明确结论。
