767P - Response rates and outcomes with enzalutamide for patients with metastatic castration resistant prostate cancer and visceral disease in the PREVAIL...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Cytotoxic agents
Prostate Cancer
Biological therapy
Presenter Celestia Higano
Citation Annals of Oncology (2014) 25 (suppl_4): iv255-iv279. 10.1093/annonc/mdu336
Authors C. Higano1, J. Alumkal2, S. Chowdhury3, Y. Loriot4, C.N. Sternberg5, J.S. De Bono6, B. Tombal7, J. Carles8, F.G. Perabo9, D. Forer10, S. Noonberg11, H. Mansbach12, T. Beer13
  • 1Seattle Cancer Care Alliance, University of Washington, 98109 - Seattle/US
  • 2Medicine, Oregon Health & Science University, Knight Cancer Institute, Portland/US
  • 3Department Of Medical Oncology, Guy's and St. Thomas' Hospital NHS Trust, SE1 9RT - London/GB
  • 4Medical Oncology, Institut de cancérologie Gustave Roussy, 94800 - Villejuif/FR
  • 5Medical Oncology, San Camillo Forlanini Hospital, Rome/IT
  • 6Oncology, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research ICR, SM25PT - Sutton/GB
  • 7Division Of Urology, Cliniques Universitaires Saint-Luc, 1200 - Brussels/BE
  • 8Department Of Oncology, Vall d'Hebron Hospitals, 08035 - Barcelona/ES
  • 9Medical Science, Astellas Pharma Global Development, US-60015 - Deerfield/US
  • 10Oncology, Medivation, San Francisco/US
  • 11Clinical Development, Medivation, Inc., San Francisco/US
  • 12Medical Affairs, Medivation, San Francisco/US
  • 13Ohsu Knight Cancer Institute, Oregon Health & Science University, Portland/US



In the PREVAIL trial, enzalutamide, an androgen receptor signaling inhibitor, significantly improved overall survival (OS) (HR, 071; p < 0.0001) and radiographic progression- free survival (rPFS) (HR, 0.19; p < 0.0001) compared to placebo in chemotherapy-naive men with metastatic castrate-resistant prostate cancer (mCRPC). Patients with visceral metastases have worse prognosis, may have a distinct biology and typically have been excluded from Phase 3 trials in chemotherapy-naïve men. Here we describe outcomes from patients with baseline visceral disease in PREVAIL.


PREVAIL was a Phase 3 multinational, double-blind study in chemotherapy-naïve men with asymptomatic or mildly symptomatic mCRPC. Co-primary endpoints were OS and rPFS. Best soft tissue objective response, a secondary endpoint, was defined as partial or complete response (PR or CR) per RECIST 1.1 criteria in patients with measurable disease at baseline.


A total of 1717 men were randomized (1715 treated) including 1513 (88.1%) without and 204 (11.9%) with visceral disease at screening (139 lung, 74 liver and 9 both). Patients with visceral disease had higher baseline median PSA than those without visceral disease (72.5 ng/mL and 46.8 ng/mL, respectively), worse performance status (38.2% and 31.1% ECOG PS = 1), and higher rates of lymph node disease (57.8% and 49.8%), but similar rates of bone disease (80.4% and 83.7%). Adverse event rates were similar to the full study population.


Visceral metastases were permitted in the PREVAIL trial of men with chemotherapy-naïve mCRPC. Enzalutamide was active in this small group of patients; post-hoc analyses showed benefit vs placebo on OS, rPFS, and secondary endpoints. Response rates were higher for lung vs liver metastases. These results support androgen receptor signaling as an important target in prostate cancer with visceral metastases.

Response Rates and Study Outcomes in PREVAIL

Total Visceral Disease Cohort Lung and/or Liver (n = 204)
Median (months) Enzalutamide/Placebo HR (95% CI)
rPFS NYR/3.6 0.28 (0.16, 0.49)
OS 27.8/22.8 0.82 (0.55, 1.23)
Time to cytotoxic chemotherapy 22.6/6.6 0.30 (0.20, 0.45)
Time to PSA progression (PCWG2 criteria) 11.1/2.9 0.16 (0.10, 0.26)
Time to first skeletal-related event 29.5/NYR 0.69 (0.43, 1.11)
Visceral Disease Cohort With Baseline Measurable Soft Tissue Disease*
Liver Lung
Enzalutamide (N= 31) Placebo (N= 28) Enzalutamide (N= 25) Placebo (N= 36)
Best Objective Response (95% CI) 29.0% (14.2-48.0) 0.0 (0.0 - 12.3) 60.0% (38.7-78.9) 0.0% (0.0- 9.7)
Complete Response 6.5% 0.0% 8.0% 0.0%
Partial Response 22.6% 0.0% 52.0% 0.0%

*Defined as at least one target lesion per RECIST 1.1.


C. Higano: Consultant: Astellas/Medivation, Bayer, Dendreon, Johnson & Johnson Research Funding: Alegra, Aragon, Astellas/Medivation, Dendreon, Sanofi; S. Chowdhury: Advisory Board/Lectures: Astellas, Janssen Cilag, Sanofi-Aventis, Dendreon Speaker: GSK; Y. Loriot: Consultant/Advisory: Astellas Research Funding: Astellas Other: Sanofi, Cellgene, Bayer, Jansen; C.N. Sternberg: Honoraria: Astellas, Johnson & Johnson, Ipsen, Bayer, Millenium; J.S. de Bono: Astellas/Medivation; B. Tombal: Advisor: Medivation, Astellas, Ferring Speaker: Astellas, Ferring; F.G. Perabo: Employee: Astellas Pharma; D. Forer, S. Noonberg and H. Mansbach: Employee: Medivation; T. Beer: Research Funding: Astellas/Medivation, Janssen Consultant: Janssen.

All other authors have declared no conflicts of interest.