Differential side effects profile in patients with mCRPC treated with abiraterone or enzalutamide: a meta-analysis of randomized controlled trials

// Raphael B. Moreira 5 , Marcio Debiasi 2,4 , Edoardo Francini 1 , Pier V. Nuzzo 1,6 , Guillermo De Velasco 1 , Fernando C. Maluf 2,3 , Andre P. Fay 2,4 , Joaquim Bellmunt 1 , Toni K. Choueiri 1 and Fabio A. Schutz 2,3 1 Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA 2 Latin American Cooperative Oncology Group, Partenon, Porto Alegre, Brazil 3 Centro Oncológico Antônio Ermírio de Moraes, Beneficencia Portuguesa de Sao Paulo, Sao Paulo, SP, Brazil 4 PUCRS School of Medicine, Porto Alegre, RS, Brazil 5 Hospital Alemão Oswaldo Cruz/Grupo Oncoclinicas do Brasil, São Paulo, SP, Brazil 6 University of Genoa, Genoa, Italy Correspondence to: Toni K. Choueiri, email: // Fabio A. Schutz, email: // Keywords : metastatic prostate cancer, abiraterone, enzalutamide, toxicity, meta-analysis Received : October 26, 2016 Accepted : March 08, 2017 Published : August 08, 2017 Abstract 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. Methods: We performed a literature search on MEDLINE for studies reporting abiraterone and enzalutamide side effects from January 1966 to July 31, 2015. Abstracts presented at ASCO meetings from 2004 to 2015 were selected manually. Phase III RCT were included in analysis. We assessed the risk of adverse events reported in RCT by performing two meta-analyses: abiraterone-prednisone vs. placebo-prednisone (2,283 pts) and enzalutamide vs. placebo (2,914 pts). Summary of incidence, relative-risks (RR), and 95% confidence intervals (CI) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: Overall, enzalutamide was not associated with all-grade (RR 1.06 - 95% CI 0.67-1.65) or grade ≥3 (RR 0.81 - 95% CI 0.28-2.33) cardiovascular events, but was associated with increased risk of all-grade fatigue (RR 1.29 - 95% CI 1.15-1.44). On the other hand, abiraterone was associated with increased risk of all-grade (RR 1.28 - 95% CI 1.06-1.55) and grade ≥3 (RR 1.76 - 95% CI 1.12-2.75) cardiovascular events, but was not associated with all-grade (RR 0.85 - 95% CI 0.58-1.23) or grade ≥3 (RR 1.07 - 95% CI 0.97-1.19) fatigue. Conclusions: In this meta-analysis, abiraterone was associated with an increased risk of cardiovascular events, while enzalutamide was associated with an increased risk of fatigue.