Comparison of pneumonia and sepsis risks between enzalutamide and abiraterone in patients with prostate cancer

<bold>Importance:</bold> Enzalutamide and abiraterone may differ in their immunomodulatory effects, and the prednisone co-administered with abiraterone can be immunosuppressive. <bold>Objective:</bold> This study aimed to compare the risk of different types of infection in prostate cancer (PCa) patients receiving enzalutamide or abiraterone in combination with ADT. <bold>Design:</bold> Retrospective cohort study. <bold>Setting:</bold> Population-based study. <bold>Participants:</bold> Patients with PCa receiving either enzalutamide or abiraterone in addition to ADT in Hong Kong between December 1999 to March 2021 were identified. They were followed up until September 2021 or censoring event including death and crossover. <bold>Exposures:</bold> Patients were divided according to enzalutamide or abiraterone use. <bold>Main outcomes and measures:</bold> Pneumonia and sepsis were analyzed as both time-to-event outcomes (multivariable Fine-Gray regression, with mortality considered a competing event) and recurrent-event outcomes (multivariable negative binomial regression). <bold>Results:</bold> 1582 patients were analyzed (abiraterone group: 923; enzalutamide group: 659) with a median follow-up of 10.6 months (interquartile range: 5.3-19.9 months). Compared to abiraterone users, enzalutamide users had lower cumulative incidences of pneumonia (aSHR 0.76 [0.59-0.99]) and sepsis (adjusted subhazard ratio [aSHR] 0.70 [0.53-0.93], p=0.014). The associations between enzalutamide use and lower risk of pneumonia may be stronger in patients ≤70 years old. <bold>Conclusions:</bold> Enzalutamide users have a significantly lower risk of pneumonia and sepsis.