Subgroup analysis of Japanese men in the PREVAIL trial of enzalutamide (ENZA) in men with chemotherapy-naïve, metastatic castration-resistant prostate cancer (mCRPC)

Date

19 Dec 2015

Session

Poster presentation 1

Presenters

Go Kimura

Citation

Annals of Oncology (2015) 26 (suppl_9): 71-79. 10.1093/annonc/mdv524

Authors

G. Kimura1, J. Yonese2, T. Fukagai3, T. Kamba4, K. Nishimura5, M. Nozawa6, T. Parli7, A. Theeuwes8, T.M. Beer9, B. Tombal10, T. Ueda11

Author affiliations

  • 1 Department Of Urology, Nippon Medical School, 113-0022 - Tokyo/JP
  • 2 Department Of Urology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo/JP
  • 3 Department Of Urology, Showa University Koto Toyosu Hospital, Tokyo/JP
  • 4 Department Of Urology, Kyoto University Hospital, Kyoto/JP
  • 5 Department Of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka/JP
  • 6 Department Of Urology, Kinki University Faculty of Medicine, Osaka/JP
  • 7 Clinical Development, Medivation Inc., San Francisco/US
  • 8 Biostatistics, Astellas Pharma Global Development Inc., Leiden/NL
  • 9 Ohsu Knight Cancer Institute, Oregon Health & Science University, Portland/US
  • 10 Division Of Urology, Cliniques Universitaires Saint-Luc, Brussels/BE
  • 11 Prostate Center And Division Of Urology, Chiba Cancer Center, Chiba/JP
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Aim/Background

PREVAIL, a multinational phase 3 randomized trial, was halted after ENZA was shown to reduce risk of radiographic progression or death by 81% and risk of death by 29% compared with placebo (PBO) in a planned interim analysis (which became the final analysis). In this post-hoc analysis, we evaluated efficacy, with an extended analysis of radiographic progression-free survival (rPFS) and overall survival (OS), safety, and pharmacokinetics of ENZA in Japanese pts.

Methods

Asymptomatic or mildly symptomatic chemotherapy-naïve pts with mCRPC progressing on androgen deprivation therapy were randomly assigned 1:1 to 160 mg/day oral ENZA or PBO until discontinuation upon unacceptable adverse event (AE), or radiographic progression or skeletal-related event and initiation of antineoplastic therapy. Coprimary endpoints were rPFS by central review and OS. Secondary endpoints included time to initiation of chemotherapy, time to prostate-specific antigen (PSA) progression and PSA response (≥50% decline). Plasma concentrations of ENZA were measured at 5, 13, and 25 weeks. Safety was analyzed in all randomized pts who received ≥1 dose of study drug.

Results

61 Japanese pts were enrolled (ENZA: 28, PBO: 33). In the final analysis, ENZA showed benefit over PBO with hazard ratios (HRs) of 0.30 for rPFS (95% confidence interval [CI]: 0.03, 2.95), 0.59 for OS (95% CI: 0.20, 1.8), 0.46 for time to chemotherapy (95% CI: 0.22, 0.96), and 0.36 for time to PSA progression (95% CI: 0.17, 0.75). PSA responses were observed in 60.7% of ENZA- vs 21.2% of PBO-treated pts. Plasma concentrations of ENZA were higher in Japanese pts: geometric mean ratio of Japanese/non-Japanese pts = 1.126 (95% CI: 1.018, 1.245) at 13 weeks. Treatment-related AEs grade ≥3 occurred in 3.6% of ENZA- and 6.1% of PBO-treated pts. With an additional 4 months of exposure for rPFS by investigator review and 10 months for OS, and with some patients who crossed over from PBO to ENZA in the open-label extension, the HRs were 0.40 (95% CI: 0.18, 0.90) and 0.65 (95% CI: 0.28, 1.51), respectively.

Conclusions

Efficacy and safety results in Japanese pts were consistent with the overall PREVAIL trial.

Clinical trial identification

NCT01212991

Disclosure

G. Kimura: grants and personal fees from Astellas, during the conduct of the study; grants and personal fees from Takeda, Pfizer, Bayer, Novartis, GlaxoSmithKline, and Ono Pharmaceutical, outside the submitted work

J. Yonese, T. Fukagai: grants from Astellas, during the conduct of the study. M. Nozawa: grants and personal fees from Astellas, during the conduct of the study. T. Parli: 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

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. 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. Ueda: other from Astellas, during the conduct of the study. All other authors have declared no conflicts of interest.

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