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 Anti-Cancer Agents & Biologic Therapy
Prostate Cancer
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.