242PD - Subgroup analysis of Asian men in the PREVAIL trial of enzalutamide (ENZA) in men with chemotherapy-naïve, metastatic castration-resistant prostat...

Date 19 December 2015
Event ESMO Asia 2015 Congress
Session Genitourinary tumours
Topics Anticancer agents
Prostate Cancer
Therapy
Biological Therapy
Presenter Edmund Chiong
Citation Annals of Oncology (2015) 26 (suppl_9): 71-79. 10.1093/annonc/mdv524
Authors C. Kim1, Y.D. Choi2, S.E. Lee3, H.M. Lee4, T. Ueda5, J. Yonese6, T. Fukagai7, E. Chiong8, W.K.O. Lau9, S. Abhyankar10, A. Theeuwes11, B. Tombal12, T.M. Beer13, G. Kimura14
  • 1Department Of Urology, Asan Medical Center, 138-736 - Seoul/KR
  • 2Department Of Urology, Severance Hospital, Seoul/KR
  • 3Department Of Urology, Seoul National University Bundang Hospital, Seoul/KR
  • 4Department Of Urology, Samsung Medical Center, Seoul/KR
  • 5Prostate Center And Division Of Urology, Chiba Cancer Center, Chiba/JP
  • 6Department Of Urology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo/JP
  • 7Department Of Urology, Showa University Koto Toyosu Hospital, Tokyo/JP
  • 8Department Of Urology, National University Hospital, Singapore/SG
  • 9Department Of Urology, Singapore General Hospital, Singapore/SG
  • 10Medical Affairs, Medivation Inc., San Francisco/US
  • 11Biostatistics, Astellas Pharma Global Development Inc., Leiden/NL
  • 12Division Of Urology, Cliniques Universitaires Saint-Luc, Brussels/BE
  • 13Ohsu Knight Cancer Institute, Oregon Health & Science University, Portland/US
  • 14Department Of Urology, Nippon Medical School, Tokyo/JP

Abstract

Aim/Background

PREVAIL, a phase 3 randomized trial, was halted after a planned interim analysis demonstrated a statistically significant improvement in overall survival (OS) for ENZA-treated men with mCRPC compared to placebo (PBO). We retrospectively evaluated efficacy, with an extended analysis of radiographic progression-free survival (rPFS) and OS, safety, and pharmacokinetic exposure of ENZA in patients from Japan and Republic of Korea.

Methods

Asymptomatic or mildly symptomatic chemotherapy-naïve patients with mCRPC progressing on androgen deprivation therapy were randomly assigned 1:1 to ENZA 160 mg/day or PBO and treated until discontinuation upon unacceptable adverse event (AE), or radiographic progression or skeletal-related event and initiation of chemotherapy. Coprimary endpoints were rPFS by central review and OS. Prostate-specific antigen (PSA) response was defined as a confirmed ≥50% reduction from baseline to nadir. Plasma concentrations of ENZA were measured at weeks 5, 13, and 25. AEs were analyzed in all randomized patients who received ≥1 dose of study drug.

Results

139 Asian patients were randomized (ENZA: 68, PBO: 71). In the final PREVAIL analysis, HRs for rPFS and OS in Asian patients were 0.30 (95%CI: 0.07-1.27) and 0.67 (95%CI: 0.32-1.41), respectively. Median time to chemotherapy was not yet reached with ENZA versus 10.4 months with PBO (HR, 0.32; 95%CI: 0.18-0.56). PSA responses were more common in patients receiving ENZA (66%) versus PBO (15%). Plasma concentrations of ENZA were slightly higher in the Asian subgroup (geometric mean Cmin = 14.7 µg/mL vs 12.1 µg/mL in non-Asian cohort at 13 weeks). AEs ≥ Grade 3 were more common with ENZA (32% vs 24% with PBO). Treatment-related AEs ≥ Grade 3 were reported in 1.5% of ENZA- and 2.8% of PBO-treated patients. In an extended analysis of rPFS determined by investigator and OS, which included 4 and 10 months of additional follow-up, respectively, HRs were 0.30 (95%CI: 0.18-0.51) and 0.69 (95%CI: 0.39-1.23).

Conclusions

Efficacy and safety results from the Asian subgroup were consistent with results from the overall PREVAIL trial.

Clinical trial identification

NCT01212991

Disclosure

T. Ueda: other from Astellas, during the conduct of the study. J. Yonese, T. Fukagai: grants from Astellas, during the conduct of the study. E. Chiong: other from National University Hospital, from null, during the conduct of the study. S. Abhyankar: personal fees from Medivation, during the conduct of the study; personal fees from Medivation, Inc, outside the submitted work. A. Theeuwes: personal fees from Astellas, during the conduct of the study; personal fees from Astellas, outside the submitted work. B. Tombal: consulting fees from Amgen, Sanofi, and Astellas for honorarium, travel support, board membership; reports personal fees from Amgen, Ferring, Bayer Sanofi for board membership, consultancy, and speaker bureaus. T.M. Beer: consulting fees: Janssen Japan, Astellas; Research funding: Astellas, Medivation, Janssen Research & Development; payment from Research to Practice in Certified Nursing Education supported by Medivation and Astellas. G. Kimura: reports grants and personal fees from Astellas, during the conduct of the study; grants and personal fees from Takeda, Pfizer, Bayer, Novartis, GlaxoSmithKline, Ono pharmaceutical, outside the submitted work. All other authors have declared no conflicts of interest.