San Francisco, CA—Both abiraterone and enzalutamide are approved by the US Food and Drug Administration for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Both drugs have different mechanisms of action and different adverse event profiles, but there are limited data comparing them directly. When choosing a therapy for mCRPC on an individualized basis, side effects are an important consideration.
A meta-analysis of phase 3 studies of these drugs in men with mCRPC showed that abiraterone was associated with an increased risk of cardiovascular events, while enzalutamide was associated with an increased risk of fatigue.1 The study was presented at the 2016 Genitourinary Cancers Symposium.
“Both drugs have similar efficacy and are well tolerated overall. The differential side effect profiles will be important for a minority of patients, particularly those with baseline comorbidities. For example, for older, frail patients with no cardiac problems, abiraterone may be better, while for those with cardiac problems, enzalutamide may be a better choice,” said senior author Fabio A. B. Schutz, MD, Antônio Ermírio de Moraes Oncology Center, Sao Paulo, Brazil.
“Older, frail patients and those with cardiovascular conditions are typically excluded from clinical trials, so we feel these findings are critical in selecting the right treatment for real-world patients. We will try to build on this work and look at more adverse events. For this analysis, we were limited to the adverse events included in published phase 3 trials,” he explained.
The authors performed a MEDLINE literature search for phase 3 studies reported from January 1966 to July 2015. They also manually selected abstracts of phase 3 studies of both drugs presented at meetings of the American Society of Clinical Oncology from 2004 to 2015. They identified 4 contemporary trials that met the inclusion criteria. Because none of the randomized controlled trials directly compared the 2 drugs, they assessed the risk of adverse events in trials that compared abiraterone plus prednisone versus placebo plus prednisone (2283 patients) and enzalutamide versus placebo (2914 patients).
Cardiac events were defined as ischemic heart disease, myocardial infarction, supraventricular tachyarrhythmias, ventricular tachyarrhythmias, cardiac failure, and possible arrhythmia-related investigations, signs, and symptoms.
Overall, enzalutamide had no association with all-grade or grade 3 or higher cardiovascular events, while it was associated with about a 30% increased risk of all-grade fatigue. On the other hand, abiraterone was associated with about a 6% increased risk of all-grade cardiovascular events and a 76% increased risk of grade 3 or higher cardiovascular events, but had no association with all-grade or grade 3 or higher fatigue.
“We found no evidence of publication bias,” Dr Schutz said. “We hope these findings can be helpful in counseling patients with regard to therapy.”
A separate analysis of the control arms of 2 randomized phase 3 trials in men with mCRPC post-docetaxel treatment (N = 794) compared adverse events with placebo versus prednisone plus placebo.2 The analysis showed that, compared with placebo alone, prednisone plus placebo did not improve overall survival, but also significantly increased the frequency of grade 3 or higher toxicities.
The authors concluded that “with the exception of use in combination with abiraterone, prednisone alone or in combination regimens should be questioned, given its unclear palliative benefits and association with increased toxicities.” Lead author was Guru Sonpavde, MD, University of Alabama at Birmingham Comprehensive Cancer Center.
1. Brandão Moreira R, Debiasi M, Maluf FC, et al. Differential side effects profile in mCRPC patients treated with abiraterone or enzalutamide: a meta-analysis of randomized controlled trials. Presented at: 2016 Genitourinary Cancers Symposium; January 7-9, 2016; San Francisco, CA. Abstract 73.
2. Sonpavde G, Pond GR, Templeton AJ, et al. Impact of single agent daily prednisone on survival and toxicities in post-docetaxel men with metastatic castration-resistant prostate cancer (mCRPC): an analysis of 2 phase III trials. Presented at: 2016 Genitourinary Cancers Symposium; January 7-9, 2016; San Francisco, CA. Abstract 213.