Skin-Related Adverse Events in Patients Treated With Apalutamide Versus Enzalutamide for Prostate Cancer: A Japanese Real-World Database Study (A Retrospective Cohort Study).

Abstract

Background and aims: Apalutamide (APA) and enzalutamide (ENZ) are androgen receptor pathway inhibitors widely used for prostate cancer. Skin rash is a characteristic adverse event of APA, but how often it occurs in real-world practice, the factors related to it, and possible differences by disease stage are not well understood.

Methods: Using a Japanese nationwide claims database (Medical Data Vision), we identified patients with prostate cancer treated with APA (240 mg/day) or ENZ (160 mg/day) between April 2008 and August 2021. A skin-related adverse event was defined as a case with both a skin-related diagnosis and treatment for the skin event during therapy. Patients were classified as mCSPC or CRPC. We compared the rate and timing of skin rash between the two drugs and between disease stages, and examined associated clinical factors.

Results: A total of 5524 patients were included (1264 APA and 4260 ENZ). The rate of skin rash was higher in the APA group than in the ENZ group (25.3% vs. 9.95%; p < 0.001), confirmed by Kaplan-Meier analysis. Within each drug, the rate did not differ significantly between mCSPC and CRPC. Most events occurred within the first month (median 29 days for APA and 22 days for ENZ). Age, body weight, BMI, and BSA were not associated with skin rash. After adjustment for age, body weight, BMI, and BSA, the risk remained about 2.6-fold higher with APA (adjusted HR: 2.56, 95% CI: 2.18-3.01).

Conclusion: Skin-related adverse events requiring treatment were more common with APA than with ENZ, but they did not differ by disease stage for either drug and were not predicted by body size. Careful skin monitoring and early intervention are important for all patients from the start of APA or ENZ treatment, regardless of disease stage.