Meta-analysis of randomized clinical trials in metastatic castration resistant prostate cancer: Comparison of hypertension, neurological and psychiatric adverse events on enzalutamide and abiraterone acetate plus prednisone treatment

Date

09 Oct 2016

Session

Poster display

Presenters

Pedro Ruiz Gracia

Citation

Annals of Oncology (2016) 27 (6): 243-265. 10.1093/annonc/mdw372

Authors

P. Ruiz Gracia1, L. Dearden2, L. Antoni3, R. Parra Gabilondo4, A. Garcia Garcia-Porrero5, M. Iznaola4

Author affiliations

  • 1 Maf Departement Oncology, Janssen Cilag, Spain, 28042 - Madrid/ES
  • 2 Health Economics And Market Access, JANSSEN PHARMACEUTICALS, HP12 4DP - Madrid/ES
  • 3 Medical, Jansen-Cilag.France, Paris/FR
  • 4 Health Economics And Market Access, JANSSEN PHARMACEUTICALS, Madrid/ES
  • 5 Maf Department Oncology, Janssen Cilag, Spain, Madrid/ES
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Background

Enzalutamide (ENZ) and abiraterone acetate (AA) are oral hormonal agents for the treatment of metastatic castration resistant prostate cancer (mCPRC) patients. Although these two drugs target the androgen signaling pathway, they have different mechanisms of action, with ENZ targeting the androgen receptor1 whilst abiraterone targeting the activity of CYP172.Consequently, they also differ in the nature of their adverse events profile

Methods

Following a meta-analysis presented at ASCO GU 20163 on fatigue and cardiovascular adverse events (AEs) a further analysis, using the same methodology, was performed on hypertension, neurological and psychiatric AEs based on a literature search of randomized controlled trials (RCTs) that included AA + prednisone (P) or ENZ. The risk of these AEs was assessed by the overall relative risk of all the RCTs that comply with the inclusion criteria. 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

RR for hypertension (all grades) was 2.26 (1.06-4.81) for ENZ and 1.61 (1.30-2.00) for AA + P, for hypertension grade ≥ 3 was 2.52 (1.61-3.95) and 1.72 (0.97-3.06) respectively. The RR for neurological disorders was 1.44 (1.31-1.58) for ENZ and 1.13 (0.99-1.29) for AA + P. RR for psychiatric disorders was 1.43 (1.21-1.69) for ENZ and 1.04 (0.9-1.20) for AA + P. No evidence of publication bias was observed.

Conclusions

The aim of this study is to contrast the hypertension, psychiatric and central nervous system disorders safety profile of AA + P and ENZ. This analysis suggests that mCRPC patients treated with ENZ had a higher risk of developing hypertension, neurological and psychiatric disorders than the patients treated with AA + P. One may speculate that the affinity of ENZ for GABA receptor may play a role in the toxicities related to the central nervous system4.

Clinical trial identification

Legal entity responsible for the study

Janssen. Spain

Funding

jannsen, Spain

Disclosure

P. Ruiz Gracia: Current employee at Janssen pharmaceuticals -Oncology dpt. L. Dearden: Current employee at Jansseńs EMEA Health economics and market research (head manager).

L. Antoni: Current employe at Janssen pharmaceuticals- MAF EMEA manager.

R. Parra Gabilondo: Current Janssen employee.

A. Garcia Garcia-Porrero: Currently Janssen employee.

M. Iznaola: Jansseńs Health economics and market access research department employee.

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