1. METHODS and STATISTICS
Differential side effects profile in mCRPC patients treated with abiraterone or enzalutamide: a meta-analysis of randomized controlled trials.
Raphael B. Moreira 1, Marcio Debiasi 2, Fernando C. Maluf 1,2, Joaquim Bellmunt 3, Andre P. Fay 2,3,4, Toni K. Choueiri 3, Fabio A. B. Schutz 1,2.
1. Centro Oncológico Antônio Ermírio de Moraes, Beneficencia Portuguesa de Sao Paulo, Sao Paulo, SP, Brazil, 2. Latin American Cooperative Oncology Group (LACOG), 3. Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA, 4. PUCRS School of Medicine, Porto Alegre, RS, Brazil.
OBJECTIVE
RESULTS
To determine the incidence and differential side effects profile in Metastatic Castration-Resistant Prostate Cancer (mCRPC) patients treated with abiraterone or enzalutamide
Table 1. Number of events reported in each trial included in the analysis.
Figure 6 - Abiraterone - Cardiac event ≥ grade 3
Figure 3 - Enzalutamide- Fatigue of any grade
BACKGROUND
Abiraterone and enzalutamide are currently approved for mCRPC patients.
Both drugs have distinct mechanisms of action and may have different toxicity profile. There are limited data comparing the side effects of abiraterone and enzalutamide. .
We performed a meta-analysis of randomized controlled trials (RCT) to better characterize the risk of adverse events associated with both drugs.
Figure 4 - Enzalutamide- Fatigue ≥ grade 3
Figure 7 - Enzalutamide- Any cardiac event
Figure 1 - Abiraterone- Fatigue of any grade
METHODS and STATISTICS
Selection of Studies:
Databases: PubMed (from January 1966 to  July 31, 2015), Abstracts presented at ASCO meetings from 2004 to 2015 were selected manually.
We assessed the risk of adverse events reported in randomized controlled trials by performing two meta-analysis: abiraterone-prednisone vs. placebo-prednisone (2283pts) and enzalutamide vs. placebo (2914pts).
Key words (1): clinical trial, randomized, abiraterone, Metastatic Castration-Resistant Prostate Cancer
Key words (2): clinical trial, randomized, enzalutamide, Metastatic Castration-Resistant Prostate Cancer
The following adverse outcomes were considered as cardiac event: ischaemic heart disease, myocardial infarction, supraventricular tachyarrhythmias, ventricular tachyarrhythmias, cardiac failure, and possible arrhythmia-related investigations, signs, and symptoms.
Inclusion criteria: randomized phase 3 trials, patients assigned to treatment with abiraterone or enzalutamide in only one arm, and adequate safety data available for adverse effect.
Statistical analysis: Stata version 9.2 software
A two-tailed p value of less than 0.05 was considered statistically significant.
Figure 5 - Abiraterone - Any cardiac event
Figure 8 - Enzalutamide- Cardiac event ≥ grade 3
Figure 2 - Abiraterone- Fatigue ≥ grade 3
CONCLUSIONS
In this meta-analysis of randomized phase 3 trials in mCRPC treated with abiraterone or enzalutmide we have observed that:
Abiraterone, but not enzalutamide, was associated with an increased risk of cardiovascular adverse events (all-grade with a RR 1.28 and grade ≥3 with a RR 1.76)
Enzalutamide, but not abiraterone, was associated with an increased risk of all-grade fatigue (RR 1.29)
Since both drugs have similar efficacy, a better understanding of the differential side effects profiles of Abiraterone and Enzalutamide is critical to help selecting the therapy for patients, in special for those with baseline comorbidities.