Lichenoid drug eruption and apalutamide: Analyses from pharmacovigilance databases and disproportionality analysis.

Abstract

Introduction: Apalutamide is an oral androgen receptor pathway inhibitor used to treat non-metastatic castration-resistant prostate cancer at high risk of developing metastases. Skin toxicity of apalutamide is documented, including a few cases of lichenoid drug eruptions (LDE). The objective of our study is to qualitatively and quantitatively describe LDE associated with apalutamide using data from the French Pharmacovigilance Database (FPVD) and Vigibase.

Methods: FPVD and Vigibase were queried on August 5, 2024, for reports of LDE associated with apalutamide. Disproportionality analysis was performed using VigiBase®, calculating the reporting odds ratio (ROR) and Bayesian confidence propagation neural network information components (IC).

Results: Qualitatively, we identified and analyzed 16 cases of apalutamide related-LDE. The average age of male patients was 75 years. The median time to LDE onset was 4 months. Clinically, LDE presented as maculopapular rashes, lichenified aspects, lichen planus, lichenoid keratosis, and psoriasiform aspects. Management typically involved apalutamide discontinuation (81,2%) and corticosteroid therapy (56,2%), with favourable outcomes in 10 cases (62,5%). Quantitatively, disproportionality analysis showed significant ROR and IC for LDE and apalutamide (ROR 6.5, 95% CI 6.0-7.0; IC 2.4, IC025 1.6-3.3).

Conclusion: Skin rash and pruritus reactions are frequently observed with apalutamide, possibly because of its chemical structure. Our qualitative and quantitative analysis of LDE cases observed among apalutamide exposed patients support a safety signal. LDE generally resolved with topical corticosteroids, but often required the discontinuation of apalutamide. When faced with a LDE, clinicians should consider exposure to apalutamide as one of the potential causes.