5PSQ-115 Evaluation of hypothyroidism associated with apalutamide and enzalutamide treatment in metastatic prostate cancer using the European adverse effect database (EudraVigilance)

Background and Importance Hypothyroidism is a limiting and underestimated adverse effect of metastatic prostate cancer treatments, the impact of which in elderly patients is more significant. Apalutamide and enzalutamide are drugs with similar chemical structure, but differ in terms of adverse effect profile. Hypothyroidism is described as a common adverse reaction for apalutamide, but has not been evaluated in pivotal trials of enzalutamide. Aim and Objectives To compare the incidence of hypothyroidism with apalutamide and enzalutamide by analysing spontaneous real-life reports obtained from EudraVigilance database. Material and Methods Spontaneous notifications concerning the evaluated drugs were obtained from EudraVigilance, the European Medicines Agency's database for suspected adverse drug reactions. For each drug-event combination, the following were calculated as measures of disproportionality: the proportional reporting ratio (PRR), the 95% confidence interval (CI95%), the Chi-square (χ²) and the number of reported cases. Among all reported adverse reactions, only those classified as hypothyroidism (event) were considered. The analysis periods were 2019–2023 for apalutamide and 2013–2023 for enzalutamide (from the date of authorisation). For the generation of an alert signal, the following 3 criteria must be met: PRR≥2, χ²≥4 and the number of new cases reported ≥3 (1). Results In the period studied, for both drugs, a total of 26.077 adverse reaction reports were collected. Of these, 4.274 (16%) were for apalutamide and 21.803 (84%) for enzalutamide, of which 74 (1.7%) and 14 (0.06%) corresponded to hypothyroidism, respectively. The values of the disproportionality measures of apalutamide with respect to enzalutamide calculated were: PRR= 26.96 (15.24–47.69), χ²=295.32 and number of hypothyroidism cases for apalutamide=74. According to these values, when all three criteria are met, a hypothyroidism alert for apalutamide would be generated. Conclusion and Relevance Our analysis performed on the EudraVigilance real-life database confirms the high incidence of hypothyroidism in patients treated with apalutamide, according to the SPARTAN and TITAN pivotal trials, compared to enzalutamide. On the other hand, a much lower incidence of hypothyroidism is evident for enzalutamide. The importance of monitoring for signs of hypothyroidism in patients treated with apalutamide is highlighted. References and/or Acknowledgements 1. Rothman KJ. The reporting odds ratio and its advantages over the proportional reporting ratio. Pharmacoepidemiol Drug Saf. 2004 Aug;13(8):519–23. Conflict of Interest No conflict of interest.