From 2011 to 2019, the two most common drugs for metastatic prostate cancer were abiraterone acetate and enzalutamide. These two agents are highly effective with improved side-effect profiles compared to chemotherapy, allowing many more patients to be treated for metastatic prostate cancer. Correspondingly, patients treated with these agents are older with more comorbid diseases, increasing the risk of adverse events.
Importantly, abiraterone and enzalutamide have separate mechanisms of action, with abiraterone inhibiting androgen biosynthesis and enzalutamide blocking the androgen receptor. Importantly, abiraterone is administered with prednisone, a corticosteroid. The different mechanisms of action and the requirement of prednisone have the potential to cause disparate efficacy and safety, thus a different rate of adverse events. Often, adverse events can help make a decision, especially outside of trials. Several studies of patients in real-world practice have shown an increased risk of hospitalization with abiraterone1 and decreased overall survival, especially in patients with cardiovascular disease or diabetes.2,3
This study by Riekhof et. al. evaluated the rate of hospitalizations of US veterans during treatment with abiraterone or enzalutamide and determined if there was a change in the rate of hospitalization after starting treatment compared to before treatment.4 There are always going to be hospitalizations for older patients with metastatic cancer, but it is important to understand how the rate changes with one drug compared to another. Also, it is likely that drugs with different mechanisms of action could have different adverse events and types of hospitalization.
The key point of the study was that the rate of hospitalizations increased 22% in patients treated with abiraterone compared to only a 3% increase in patients treated with enzalutamide. Furthermore, patients treated with abiraterone had increased rates of hospitalization for certain cardiovascular conditions, which has been seen in prior studies.1,2 We also found something new, patients treated with abiraterone had higher rates of several types of infections, including urinary tract infections, pneumonia, and sepsis. We hypothesize that the increased rate of infections is a result of the use of prednisone with abiraterone. Prednisone may suppress the immune system and increase vulnerability to infections. The drug may impair the response to infection due to adrenal insufficiency, resulting in increased severity of infection.
Due to the retrospective, observational nature of this study, it is not possible to say that either drug caused a change in hospitalizations. However, this study supports other research that could inform treatment. In situations where clinicians and patients have options, assessment of frailty, comorbid disease, and risk of hospitalizations may guide drug choice for metastatic prostate cancer.3-5 In a clinical situation that lacks randomized data, a meta-analysis of randomized trials and real-world studies provide the best evidence available to inform treatment selection.
Written by: Martin Schoen, MD, MPH, Saint Louis Veterans Affairs Medical Center; Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, MO
References:
- Lu-Yao G, Nikita N, Keith SW, et al. Mortality and Hospitalization Risk Following Oral Androgen Signaling Inhibitors Among Men with Advanced Prostate Cancer by Pre-existing Cardiovascular Comorbidities. European urology. 2020;77(2):158-166.
- Scailteux LM, Campillo-Gimenez B, Kerbrat S, et al. Overall Survival Among Chemotherapy-Naive Patients With Castration-Resistant Prostate Cancer Under Abiraterone Versus Enzalutamide: A Direct Comparison Based on a 2014-2018 French Population Study (the SPEAR Cohort). Am J Epidemiol. 2021;190(3):413-422.
- Schoen MW, Carson KR, Eisen SA, et al. Survival of veterans treated with enzalutamide and abiraterone for metastatic castrate resistant prostate cancer based on comorbid diseases. Prostate Cancer Prostatic Dis. 2022.
- Riekhof F, Yan Y, Bennett CL, et al. Hospitalizations Among Veterans Treated for Metastatic Prostate Cancer With Abiraterone or Enzalutamide. Clinical genitourinary cancer. 2023.
- Deol ES, Sanfilippo KM, Luo S, et al. Frailty and survival among veterans treated with abiraterone or enzalutamide for metastatic castration-resistant prostate cancer. J Geriatr Oncol. 2023;14(5):101520.