766PD - Long-term efficacy and safety of enzalutamide monotherapy in hormone-naive prostate cancer: 2-year follow-up

Date 28 September 2014
Event ESMO 2014
Session Genitourinary tumours, prostate
Topics Anticancer Agents
Prostate Cancer
Biological Therapy
Presenter Bertrand Tombal
Citation Annals of Oncology (2014) 25 (suppl_4): iv255-iv279. 10.1093/annonc/mdu336
Authors B. Tombal1, M. Borre2, P. Rathenborg3, P. Werbrouck4, H. van Poppel5, A. Heidenreich6, P. Iversen7, J. Braeckman8, J. Heracek9, E. Baskin-Bey10, T. Ouatas11, F.G. Perabo12, D. Phung13, B. Baron10, M. Hirmand14, M.R. Smith15
  • 1Urology, Cliniques Universitaires St. Luc, 1200 - Brussels/BE
  • 2Medicine, Aarhus University Hospital, Aarhus/DK
  • 3Urology, Herlev Hospital, Herlev/DK
  • 4Urology, AZ Groeninge Kortrijk, Kortrijk/BE
  • 5Department Of Urology, University Hospital Gasthuisberg, BE-3000 - Leuven/BE
  • 6Urology, RWTH Aachen University, 50274 - Aachen/DE
  • 7Urology, Rigshospitalet, Copenhague/DK
  • 8Urology, UZ Brussels, Brussels/BE
  • 9Urology, Univerzita Karlova v Praze, Prague/CZ
  • 10Global Development, Astellas Pharma, Leidendorp/NL
  • 11Explocatory Development, Astellas Pharma, Leiderdorp/NL
  • 12Medical Science, Astellas Pharma Global Development, US-60015 - Deerfield/US
  • 13Global Development, Astellas Pharma, Northbrook/US
  • 14Clinical Development, Medivation, US-94105 - San Francisco/US
  • 15Hematology-oncology, Massachusetts General Hospital, 02114 - Boston/US



Androgen-deprivation therapy (ADT) is the first-choice treatment for advanced prostate cancer (PC). Enzalutamide (ENZ) is approved for the treatment of post-docetaxel metastatic castration-resistant PC. In previous analyses of a Phase 2 study in pts with hormone-naive PC (HNPC) eligible for ADT, ENZ monotherapy after 6 mos and 1 yr (49 wks) was associated with a high prostate-specific antigen (PSA) response rate regardless of presence of metastatic disease at baseline, and with stable bone mineral density (BMD) and quality of life (QoL) on treatment. Here we report long-term efficacy and safety in pts treated up to 2 yrs (wk 97).


67 patients with HNPC and noncastrate testosterone (≥230 ng/dL) were enrolled in this open-label single-arm study (NCT01302041) and received ENZ 160 mg/d until disease progression or unacceptable toxicity. The primary variable of PSA response (≥80% decline from baseline) was assessed at 6 mos, 1 yr, and 2 yrs. Additional endpoints included best overall objective tumour response, BMD, body composition, QoL and safety.


67 pts were treated. Median age was 73.0 yrs (range 48-86); 26 (38.8%) had metastatic disease at baseline, and 24 (35.8%) and 16 (23.9%) had prior prostatectomy and radiation, respectively. 4 pts discontinued during the second year of follow-up and 45 remained on ENZ at 2 yrs. PSA response rate in pts remaining on ENZ at 2 yrs was 100% (95% CI 92, 100). Of 26 pts with metastases at baseline, 13 (50%) had complete response and 4 (15.4%) partial response as best overall tumour response over 2 yrs. There were decreases in mean (SD) total body BMD of -0.39% (2.24) and lean body mass -5.27% (3.66) at 2 yrs. EORTC-QLQ C30 QoL data showed maintenance of global health status through 2 yrs, though there were clinically meaningful deteriorations (≥10 points) on the fatigue, and role functioning scales. Most common adverse events (AEs) were gynaecomastia, fatigue, nipple pain and hot flush.


ENZ monotherapy was associated with significant long-term PSA reductions and good tumour response in men with HNPC. This was achieved without adversely affecting total body BMD or global health status.


B. Tombal: has received consultancy fees from Astellas, Medivation, Amgen, and Sanofi Aventis; payment for speaker bureaus from Amgen, Sanofi Aventis, Ferring, and Bayer (for whom he is also a board member); and travel support from Astellas and Medivation; M. Borre: has received payment for speaker bureaus from Astellas and Janssen; is a member of a Medivation study Steering committee and has received consultancy fees from Astellas, Ferring and Sanofi Aventis; P. Rathenborg: has received research grant support paid to his institution from Astellas and Medivation; A. Heidenreich: has received consultancy fees and payment for speaker bureaus from Amgen, Jansen, Ipsen, Sanofi Aventis, and Takeda (for whom he is also a board member); research and travel support from Astellas, and a research grant from Sanofi Aventis;

P. Iversen: Research grant support from Astellas and Medivation; travel support for meetings related to the study from Astellas and Medivation; honoraria from Astellas and Medivation; and consultancy fees from Janssen, Ferring and Sanofi-Aventis; J. Braeckman: has received payment for speaker bureaus from Amgen and Eli Lilly; E. Baskin-Bey, T. Ouatas, F.G. Perabo, D. Phung and B. Baron: Employee of Astellas;

M. Hirmand: is an employee of Medivation and owns stock in Medivation; M.R. Smith: has received consultancy fees from Astellas, Medivation, Janssen, Aragon, and Millenium. All other authors have declared no conflicts of interest.