Enzalutamide in Japanese patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer

A post-hoc analysis of the placebo-controlled PREVAIL trial

Go Kimura, Junji Yonese, Takashi Fukagai, Tomomi Kamba, Kazuo Nishimura, Masahiro Nozawa, Hank Mansbach, Ad Theeuwes, Tomasz (Tom) Beer, Bertrand Tombal, Takeshi Ueda

    Research output: Contribution to journalArticle

    12 Citations (Scopus)

    Abstract

    Objectives: To evaluate the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients. Methods: This was a post-hoc analysis of the phase 3, double-blind, placebo-controlled PREVAIL trial. Asymptomatic or mildly symptomatic chemotherapy-naïve patients with metastatic castration-resistant prostate cancer progressing on androgen deprivation therapy were randomized one-to-one to 160 mg/day oral enzalutamide or placebo until discontinuation on radiographic progression or skeletal-related event and initiation of subsequent antineoplastic therapy. Coprimary end-points were centrally assessed radiographic progression-free survival and overall survival. Secondary end-points were investigator-assessed radiographic progression-free survival, time to initiation of chemotherapy, time to prostate-specific antigen progression, prostate-specific antigen response (≥50% decline) and time to skeletal-related event. Results: Of 1717 patients, 61 were enrolled in Japan (enzalutamide, n = 28; placebo, n = 33); hazard ratios (95% confidence interval) of 0.30 for centrally assessed radiographic progression-free survival (0.03-2.95), 0.59 for overall survival (0.20-1.8), 0.46 for time to chemotherapy (0.22-0.96) and 0.36 for time to prostate-specific antigen progression (0.17-0.75) showed the treatment benefit of enzalutamide over the placebo. Prostate-specific antigen responses were observed in 60.7% of enzalutamide-treated men versus 21.2% of placebo-treated men. Plasma concentrations of enzalutamide were higher in Japanese patients: the geometric mean ratio of Japanese/non-Japanese patients was 1.126 (90% confidence interval 1.018-1.245) at 13 weeks. Treatment-related adverse events grade ≥3 occurred in 3.6% of enzalutamide- and 6.1% of placebo-treated Japanese patients. Conclusion: Treatment effects and safety in Japanese patients were generally consistent with the overall results from PREVAIL.

    Original languageEnglish (US)
    Pages (from-to)395-403
    Number of pages9
    JournalInternational Journal of Urology
    Volume23
    Issue number5
    DOIs
    StatePublished - May 1 2016

    Fingerprint

    Castration
    Prostatic Neoplasms
    Placebos
    Drug Therapy
    Prostate-Specific Antigen
    Disease-Free Survival
    Therapeutics
    Confidence Intervals
    Safety
    Survival
    MDV 3100
    Antineoplastic Agents
    Androgens
    Japan
    Pharmacokinetics
    Research Personnel

    Keywords

    • Antineoplastic agents
    • Disease-free survival
    • Japan
    • MDV 3100
    • Prostatic neoplasms, castration-resistant

    ASJC Scopus subject areas

    • Urology

    Cite this

    Enzalutamide in Japanese patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer : A post-hoc analysis of the placebo-controlled PREVAIL trial. / Kimura, Go; Yonese, Junji; Fukagai, Takashi; Kamba, Tomomi; Nishimura, Kazuo; Nozawa, Masahiro; Mansbach, Hank; Theeuwes, Ad; Beer, Tomasz (Tom); Tombal, Bertrand; Ueda, Takeshi.

    In: International Journal of Urology, Vol. 23, No. 5, 01.05.2016, p. 395-403.

    Research output: Contribution to journalArticle

    Kimura, Go ; Yonese, Junji ; Fukagai, Takashi ; Kamba, Tomomi ; Nishimura, Kazuo ; Nozawa, Masahiro ; Mansbach, Hank ; Theeuwes, Ad ; Beer, Tomasz (Tom) ; Tombal, Bertrand ; Ueda, Takeshi. / Enzalutamide in Japanese patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer : A post-hoc analysis of the placebo-controlled PREVAIL trial. In: International Journal of Urology. 2016 ; Vol. 23, No. 5. pp. 395-403.
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    abstract = "Objectives: To evaluate the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients. Methods: This was a post-hoc analysis of the phase 3, double-blind, placebo-controlled PREVAIL trial. Asymptomatic or mildly symptomatic chemotherapy-na{\"i}ve patients with metastatic castration-resistant prostate cancer progressing on androgen deprivation therapy were randomized one-to-one to 160 mg/day oral enzalutamide or placebo until discontinuation on radiographic progression or skeletal-related event and initiation of subsequent antineoplastic therapy. Coprimary end-points were centrally assessed radiographic progression-free survival and overall survival. Secondary end-points were investigator-assessed radiographic progression-free survival, time to initiation of chemotherapy, time to prostate-specific antigen progression, prostate-specific antigen response (≥50{\%} decline) and time to skeletal-related event. Results: Of 1717 patients, 61 were enrolled in Japan (enzalutamide, n = 28; placebo, n = 33); hazard ratios (95{\%} confidence interval) of 0.30 for centrally assessed radiographic progression-free survival (0.03-2.95), 0.59 for overall survival (0.20-1.8), 0.46 for time to chemotherapy (0.22-0.96) and 0.36 for time to prostate-specific antigen progression (0.17-0.75) showed the treatment benefit of enzalutamide over the placebo. Prostate-specific antigen responses were observed in 60.7{\%} of enzalutamide-treated men versus 21.2{\%} of placebo-treated men. Plasma concentrations of enzalutamide were higher in Japanese patients: the geometric mean ratio of Japanese/non-Japanese patients was 1.126 (90{\%} confidence interval 1.018-1.245) at 13 weeks. Treatment-related adverse events grade ≥3 occurred in 3.6{\%} of enzalutamide- and 6.1{\%} of placebo-treated Japanese patients. Conclusion: Treatment effects and safety in Japanese patients were generally consistent with the overall results from PREVAIL.",
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    author = "Go Kimura and Junji Yonese and Takashi Fukagai and Tomomi Kamba and Kazuo Nishimura and Masahiro Nozawa and Hank Mansbach and Ad Theeuwes and Beer, {Tomasz (Tom)} and Bertrand Tombal and Takeshi Ueda",
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    T2 - A post-hoc analysis of the placebo-controlled PREVAIL trial

    AU - Kimura, Go

    AU - Yonese, Junji

    AU - Fukagai, Takashi

    AU - Kamba, Tomomi

    AU - Nishimura, Kazuo

    AU - Nozawa, Masahiro

    AU - Mansbach, Hank

    AU - Theeuwes, Ad

    AU - Beer, Tomasz (Tom)

    AU - Tombal, Bertrand

    AU - Ueda, Takeshi

    PY - 2016/5/1

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    N2 - Objectives: To evaluate the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients. Methods: This was a post-hoc analysis of the phase 3, double-blind, placebo-controlled PREVAIL trial. Asymptomatic or mildly symptomatic chemotherapy-naïve patients with metastatic castration-resistant prostate cancer progressing on androgen deprivation therapy were randomized one-to-one to 160 mg/day oral enzalutamide or placebo until discontinuation on radiographic progression or skeletal-related event and initiation of subsequent antineoplastic therapy. Coprimary end-points were centrally assessed radiographic progression-free survival and overall survival. Secondary end-points were investigator-assessed radiographic progression-free survival, time to initiation of chemotherapy, time to prostate-specific antigen progression, prostate-specific antigen response (≥50% decline) and time to skeletal-related event. Results: Of 1717 patients, 61 were enrolled in Japan (enzalutamide, n = 28; placebo, n = 33); hazard ratios (95% confidence interval) of 0.30 for centrally assessed radiographic progression-free survival (0.03-2.95), 0.59 for overall survival (0.20-1.8), 0.46 for time to chemotherapy (0.22-0.96) and 0.36 for time to prostate-specific antigen progression (0.17-0.75) showed the treatment benefit of enzalutamide over the placebo. Prostate-specific antigen responses were observed in 60.7% of enzalutamide-treated men versus 21.2% of placebo-treated men. Plasma concentrations of enzalutamide were higher in Japanese patients: the geometric mean ratio of Japanese/non-Japanese patients was 1.126 (90% confidence interval 1.018-1.245) at 13 weeks. Treatment-related adverse events grade ≥3 occurred in 3.6% of enzalutamide- and 6.1% of placebo-treated Japanese patients. Conclusion: Treatment effects and safety in Japanese patients were generally consistent with the overall results from PREVAIL.

    AB - Objectives: To evaluate the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients. Methods: This was a post-hoc analysis of the phase 3, double-blind, placebo-controlled PREVAIL trial. Asymptomatic or mildly symptomatic chemotherapy-naïve patients with metastatic castration-resistant prostate cancer progressing on androgen deprivation therapy were randomized one-to-one to 160 mg/day oral enzalutamide or placebo until discontinuation on radiographic progression or skeletal-related event and initiation of subsequent antineoplastic therapy. Coprimary end-points were centrally assessed radiographic progression-free survival and overall survival. Secondary end-points were investigator-assessed radiographic progression-free survival, time to initiation of chemotherapy, time to prostate-specific antigen progression, prostate-specific antigen response (≥50% decline) and time to skeletal-related event. Results: Of 1717 patients, 61 were enrolled in Japan (enzalutamide, n = 28; placebo, n = 33); hazard ratios (95% confidence interval) of 0.30 for centrally assessed radiographic progression-free survival (0.03-2.95), 0.59 for overall survival (0.20-1.8), 0.46 for time to chemotherapy (0.22-0.96) and 0.36 for time to prostate-specific antigen progression (0.17-0.75) showed the treatment benefit of enzalutamide over the placebo. Prostate-specific antigen responses were observed in 60.7% of enzalutamide-treated men versus 21.2% of placebo-treated men. Plasma concentrations of enzalutamide were higher in Japanese patients: the geometric mean ratio of Japanese/non-Japanese patients was 1.126 (90% confidence interval 1.018-1.245) at 13 weeks. Treatment-related adverse events grade ≥3 occurred in 3.6% of enzalutamide- and 6.1% of placebo-treated Japanese patients. Conclusion: Treatment effects and safety in Japanese patients were generally consistent with the overall results from PREVAIL.

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    KW - Japan

    KW - MDV 3100

    KW - Prostatic neoplasms, castration-resistant

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