Abstract
Enzalutamide is an oral androgen receptor inhibitor that targets multiple steps in the androgen receptor signaling pathway. In the randomized phase III AFFIRM study, significant improvements in survival versus placebo were observed when enzalutamide was used as a treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) following prior treatment with docetaxel. Additional benefits included significant delay in time to first skeletal-related event, and improvement in several measures of pain and health-related quality of life. Treatment effects were consistent across all prespecified subgroups. The phase III PREVAIL study evaluated enzalutamide versus placebo in patients with mCRPC who had not received chemotherapy. Enzalutamide significantly decreased the risk of radiographic progression and death. There were also significant improvements in all secondary and prespecified exploratory endpoints, including delayed initiation of chemotherapy, reduction in risk of first skeletal-related event and a high percentage of patients with objective response compared with placebo. Enzalutamide was also studied in hormone naïve patients (as monotherapy) in a small, open-label phase II study in patients with prostate cancer who were eligible for androgen-deprivation therapy. A prostate-specific antigen (PSA) response, defined as ⩾80% decline in PSA level from baseline at week 25, was achieved in 92.5% of patients. Long-term follow up is ongoing. Despite differences between these three trials, enzalutamide displayed a favorable safety profile in all three patient populations. Similar rates of adverse events between the enzalutamide and placebo groups were observed in AFFIRM and PREVAIL, with fatigue, diarrhea, back pain and hot flashes being more common with enzalutamide than with placebo. Hypertension was reported at a higher rate in the enzalutamide group than in the placebo group in PREVAIL. Breast-related disorders associated with enzalutamide treatment were also reported in the Monotherapy trial. Few seizures were reported in any trial. Enzalutamide is being studied in several early disease state populations.
| Original language | English |
|---|---|
| Journal | Therapeutic Advances in Urology |
| Volume | 7 |
| Issue number | 1 |
| Pages (from-to) | 9-21 |
| Number of pages | 13 |
| ISSN | 1756-2872 |
| DOIs | |
| Publication status | Published - 01.01.2015 |
Funding
Efficacy and safety of enzalutamide established in the AFFIRM trial led to approval in the United States and Europe for its use in patients with mCRPC after failure of docetaxel. The PREVAIL study data led to the recent approval of enzalutamide for use in chemo-naïve patients in the United States. Ongoing and planned trials will help further define the optimal use of enzalutamide in the treatment of prostate cancer. The authors would like to thank Karen Brayshaw, PhD, at Complete HealthVizion, for assistance with writing and revising the draft manuscript, based on detailed discussion and feedback from all authors. Writing assistance was funded by Astellas Pharma, Inc and Medivation, Inc. Primary responsibility for opinions, conclusions, and interpretation of data lies with the authors. All authors read and approved the final version of this manuscript. Conflict of interest statement A.S.M. has received consulting fees from Medivation, Astellas, Janssen-Cilag, Bayer, Roche, Ipsen, Novartis, and Amgen, and payment for speaker bureau from Novartis, Bayer, Janssen-Cilag, Astellas, Ipsen, GlaxoSmithKline, Hexal and Amgen. G.P.H. is an employee of Astellas. C.-A.vK. has received consulting fees from Janssen-Cilag, Teva and Astellas. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
