Investig Clin Urol.  2016 May;57(3):174-183. 10.4111/icu.2016.57.3.174.

The PREVAIL trial of enzalutamide in men with chemotherapy-naïve, metastatic castration-resistant prostate cancer: Post hoc analysis of Korean patients

• Kim CS
• Theeuwes A
• Kwon DD
• Choi YD
• Chung BH
• Lee HM
• Lee KH
• Lee SE

• KMID: 2426491
• DOI: http://doi.org/10.4111/icu.2016.57.3.174

Abstract

PURPOSE
This post hoc analysis evaluated treatment effects, safety, and pharmacokinetics of enzalutamide in Korean patients in the phase 3, double-blind, placebo-controlled PREVAIL trial.
MATERIALS AND METHODS
Asymptomatic or mildly symptomatic chemotherapy-naive men with metastatic castration-resistant prostate cancer that progressed on androgen deprivation therapy received 160 mg/d oral enzalutamide or placebo (1:1) until death or discontinuation due to radiographic progression or skeletal-related event and initiation of subsequent therapy. Coprimary end points were centrally assessed radiographic progression-free survival (rPFS) and overall survival (OS). Secondary end points included investigator-assessed rPFS, time to initiation of chemotherapy, time to prostate-specific antigen (PSA) progression, PSA response (≥50% decline), and time to skeletal-related event.
RESULTS
Of 1,717 total patients, 78 patients were enrolled in Korea (enzalutamide, n=40; placebo, n=38). Hazard ratios (95% confidence interval) for enzalutamide versus placebo were 0.23 (0.02-2.24) for centrally assessed rPFS, 0.77 (0.28-2.15) for OS, 0.21 (0.08-0.51) for time to chemotherapy, and 0.31 (0.17-0.56) for time to PSA progression. A PSA response was observed in 70.0% of enzalutamide-treated and 10.5% of placebo-treated Korean patients. Adverse events of grade ≥3 occurred in 33% of enzalutamide-treated and 11% of placebo-treated Korean patients, with median treatment durations of 13.0 and 5.1 months, respectively. At 13 weeks, the plasma concentration of enzalutamide plus N-desmethyl enzalutamide was similar in Korean and non-Korean patients (geometric mean ratio, 1.04; 90% confidence interval, 0.97-1.10).
CONCLUSIONS
In Korean patients, treatment effects and safety of enzalutamide were consistent with those observed in the overall PREVAIL study population (ClinicalTrials.gov Identifier: NCT01212991).

Keyword

Antineoplastic agents; Castration-resistant prostatic neoplasms; Disease-free survival; MDV 3100; Republic of Korea

MeSH Terms

Adenocarcinoma/blood/diagnostic imaging/drug therapy/*secondary
Administration, Oral
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Hormonal/adverse effects/blood/*therapeutic use
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Disease Progression
Double-Blind Method
Humans
Kallikreins/blood
Male
Middle Aged
Phenylthiohydantoin/adverse effects/*analogs & derivatives/blood/therapeutic use
Prostate-Specific Antigen/blood
Prostatic Neoplasms, Castration-Resistant/blood/diagnostic imaging/*drug therapy
Radiography
Survival Analysis
Treatment Outcome
Antineoplastic Agents, Hormonal
Phenylthiohydantoin
Kallikreins
Prostate-Specific Antigen

Figure

• 

  Fig. 1 PREVAIL patient disposition. ITT, intent-to-treat; rPFS, radiographic progression-free survival. *Randomization was stratified by study site.

• 

  Fig. 2 Duration of centrally assessed rPFS in Korean patients and the overall study population (data cutoff May 6, 2012). Dashed horizontal line indicates median. Hazard ratios are based on unstratified Cox regression models with treatment as the only covariate and values <1.00 favoring enzalutamide. CI, confidence interval; ENZA, enzalutamide; HR, hazard ratio; ITT, intent-to-treat; NYR, not yet reached; PBO, placebo; rPFS, radiographic progression-free survival.

• 

  Fig. 3 Duration of investigator-assessed rPFS in Korean patients (data cutoff September 16, 2013). Dashed horizontal line indicates median. Hazard ratios are based on unstratified Cox regression models with treatment as the only covariate and values <1.00 favoring enzalutamide. CI, confidence interval; ENZA, enzalutamide; HR, hazard ratio; ITT, intent-to-treat; NYR, not yet reached; PBO, placebo; rPFS, radiographic progression-free survival.

• 

  Fig. 4 Duration of OS in Korean patients and the overall study population (data cutoff Sep 16, 2013). Dashed horizontal line indicates median. Hazard ratios are based on unstratified Cox regression models with treatment as the only covariate and values <1.00 favoring enzalutamide. CI, confidence interval; ENZA, enzalutamide; HR, hazard ratio; ITT, intent-to-treat; NYR, not yet reached; OS, overall survival; PBO, placebo.

• 

  Fig. 5 Updated analysis of OS in Korean patients (data cutoff June 1, 2014). Dashed horizontal line indicates median. Hazard ratios are based on unstratified Cox regression models with treatment as the only covariate and values <1.00 favoring enzalutamide. CI, confidence interval; ENZA, enzalutamide; HR, hazard ratio; ITT, intent-to-treat; NYR, not yet reached; OS, overall survival; PBO, placebo.

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