Introduction. Original Article: Clinical Investigation

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1 bs_bs_banner International Journal of Urology (2014) 21, doi: /iju Original Article: Clinical Investigation Abiraterone acetate and prednisolone for metastatic castration-resistant prostate cancer failing androgen deprivation and docetaxel-based chemotherapy: A phase II bridging study in Korean and Taiwanese patients Cheol Kwak, 1 Tony Tong Lin Wu, 2 Hyun Moo Lee, 3 Hsi Chin Wu, 4 Sung Joon Hong, 5 Yen Chuan Ou, 6 Seok Soo Byun, 7 Hyou Young Rhim, 8 Thian Kheoh, 8 Ying Wan, 8 Howard Yeh, 8 Margaret K Yu 8 and Choung Soo Kim 9 1 Department of Urology, Seoul National University Hospital, Seoul, Korea; 2 Division of Urology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 3 Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 4 Department of Urology, China Medical University Hospital, China Medical University, Taichung, Taiwan; 5 Department of Urology, Yonsei University College of Medicine, Seoul, Korea; 6 Taichung Veterans General Hospital, Taichung, Taiwan; 7 Department of Urology, Seoul National University Bundang Hospital, Seongnam, Korea; 8 Janssen Research & Development, Raritan, New Jersey, USA; and 9 Department of Urology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Korea Abbreviations & Acronyms AE = adverse events ALT = alanine transaminase AR = androgen receptor AST = aspartate transaminase CI = confidence interval CRPC = castration-resistant prostate cancer CYP = cytochrome P-450 DHEA-S = dehydroepiandrosterone sulfate ECG = electrocardiogram ECOG = Eastern Cooperative Oncology Group LHRH = luteinizing hormone releasing hormone mcrpc = metastatic castration-resistant prostate cancer ORR = objective radiographic response rate PSA = prostate-specific antigen PSAWG = Prostate-Specific Antigen Working Group RECIST = Response Evaluation Criteria in Solid Tumors SAE = serious adverse events TEAE = treatment-emergent adverse events TURP = transurethral resection of the prostate Correspondence: Cheol Kwak M.D., Ph.D., Department of Urology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul , Korea. mdrafael@snu.ac.kr Received 17 February 2014; accepted 7 July Online publication 6 August 2014 Objectives: To evaluate the safety and efficacy of abiraterone acetate and prednisolone in Korean and Taiwanese patients with metastatic castration-resistant prostate cancer not responding to docetaxel-based chemotherapy. Methods: In this single-arm study, 82 metastatic castration-resistant prostate cancer patients who failed docetaxel-based chemotherapy were treated with abiraterone (1000 mg, once daily) and prednisolone (5 mg, twice daily). Patients achieving a prostate-specific antigen decline 50% were considered as responding. Results: A total of 35 patients (43%) achieved prostate-specific antigen response (95% confidence interval 32 54). The median time to prostate-specific antigen progression was 4.7 months (95% confidence interval ); the median overall survival was 11.8 months. Two (4%) of 50 patients with measurable disease achieved partial response. The median testosterone concentration was in the castration range (1.21 nmol/l) throughout the treatment period. Median dehydroepiandrosterone sulfate decreased from μmol/l (baseline) to μmol/l (cycle 4). The most common adverse event was bone pain (20%); grade 3/4 adverse event of special interest were hypokalemia (7%), fluid retention and liver function abnormalities (5% each), hypertension (2%), and cardiac disorders (1%). Conclusions: A combination of abiraterone acetate and prednisolone appears to be a favorable second-line treatment in Taiwanese and Korean patients with advanced metastatic castration-resistant prostate cancer after failed docetaxel-based chemotherapy. Key words: abiraterone acetate, docetaxel, metastatic castration-resistant prostate cancer, prednisolone, prostate-specific antigen. Introduction There has been a rapid rise in the incidence of prostate cancer in several Asian countries, including Japan, Taiwan, Singapore, Malaysia and the Philippines, with prostate cancer steadily becoming one of the leading cancers in Asian men. 1 In Taiwan, the incidence of prostate cancer has been rapidly increasing in the past 15 years (eight cases per 105 men in 1994; 14 cases per 105 men in 1997; 34 cases per 105 men in 2009). In 2009, there were 4013 newly diagnosed patients and 936 deaths reported, making prostate cancer the fifth most common cancer in Taiwanese men. 2,3 Similarly, the incidence of prostate cancer in Korean men is soaring (12.8%, annually) compared with other cancers. 4 According to the data analyses from the Korea Central Cancer Registry, the 5-year relative survival rate of prostate cancer in Korean men is lower compared with that found in men of the USA (90.2% vs 99.2%), and a lower number of patients (54% vs 82%) tend to be diagnosed at a localized stage The Japanese Urological Association 1239

2 CKWAKET AL. Prostate cancers are androgen-driven malignancies dependent on androgen through activation of the AR for growth. Medical or surgical castration for treatment of recurrent or advanced disease leads to removal of the testicular sources of androgens, and results in reductions in PSA concentrations and antitumor responses. Recent evidence suggests that CRPC is still stimulated by the low levels of adrenal and intratumoral (autocrine) sources of androgen. 6 8 Further inhibition of androgen production by both malignant and benign extratesticular sources can be expected to control CRPC progression, even after resistance to primary androgen deprivation has occurred. Abiraterone acetate, a selective androgen biosynthesis inhibitor, potently blocks persistent androgen synthesis from adrenal and intratumoral (autocrine/paracrine) sources, and inhibits an important driver of mcrpc progression. 9,10 It has shown clinical benefits in patients with mcrpc, with a minimal risk. 7,11 Abiraterone inhibits CYP17, a dual function enzyme that is necessary for testosterone synthesis. 10 Abiraterone in combination with prednisolone has shown to prolong overall survival in both, chemotherapy-naïve and postchemotherapy patients. 7,12 14 Although the efficacy and safety profile of abiraterone have been characterized predominately in the Caucasian population in a phase III study carried out in North America, Europe and Australia, 11,15 little is known regarding its efficacy and safety in the Asian population, as Asians accounted for a very small ( 5%) percentage of the clinical trial. Differences in race and ethnicity could have had an impact on the treatment response and safety. The present study was designed to provide clinical data on the safety and efficacy of abiraterone acetate plus prednisolone in an Asian population in Korea and Taiwan, with mcrpc who had progressive disease after docetaxel-based chemotherapy. The primary objective of the study was to determine the proportion of patients achieving a PSA decline of 50% (PSA response) according to the PSAWG criteria. 16 The secondary objective was to evaluate the safety and tolerability of abiraterone acetate plus prednisolone in these patients. Methods Patients Patients aged 18 years with mcrpc and disease progression after failed docetaxel-based chemotherapy were enrolled. These patients had confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology; PSA progression as per the PSAWG criteria; 16 PSA value 5 ng/ml, despite medical or surgical castration or prostate cancer progression as per the RECIST; 17 testosterone levels <50 ng/dl (<1.7 nmol/l); ECOG performance status 2; and adequate hematological and biochemical indices. In patients treated with LHRH agonists, the therapy was initiated at least 4 weeks before day 1 and was continued throughout the study. Key exclusion criteria included: serious or uncontrolled coexistent non-malignant disease (including active and uncontrolled infection); abnormal liver function (AST or ALT <2.5 times the upper limits of normal); uncontrolled hypertension; active or symptomatic viral hepatitis or chronic liver disease; brain metastasis; pituitary or adrenal dysfunction; clinically significant heart disease; gastrointestinal disorders and malignancy within the previous 5 years, other than basal cell or squamous cell carcinomas of skin with a >30% probability of recurrence within 12 months. Patients who were treated prior with other AR or cytochrome P450 (CYP17) inhibitor(s), or ketoconazole were also excluded from the study. Medications prohibited during the study included: 5 α-reductase inhibitor, ketoconazole, diethylstilbestrol, PC-SPES (a proprietary herbal mixture) and other preparations that would have endocrine effects on prostate cancer; radiopharmaceuticals, such as strontium or samarium; aldactone, spironol (spironolactone), fludrocortisones, digoxin, pomegranate juice or supplements; indole-3-carbinol, flaxseed oil, black cohosh and androgens (non-steroidal [bicalutamide, flutamide, nilutamide] and steroidal [megestrol acetate]); and cyproterone acetate. Patients on a stable dose of bisphosphonate were allowed to participate in the study. Initiating bisphosphonate therapy or adjusting bisphosphonate dose per regimen within 30 days before the study was prohibited; however, its initiation during the study was allowed in case a patient experienced a skeletal-related event (pathological fracture, spinal cord compression, radiation therapy or surgery to bone) attributed to metastatic bone disease. The study was carried out in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with Good Clinical Practices, applicable regulatory requirements and in compliance with the study protocol. The study protocol was reviewed and approved by the institutional review board. All enrolled participants provided written consent for participation in the study. Study design This multicenter, open-label, single-arm, phase II study, carried out in Korea and Taiwan, consisted of a screening period (within 28 days before cycle 1, day 1), treatment period (starting from the first dose of study drug to the end-of-treatment evaluation) and a follow-up period (follow up for survival every 3 months, up to 60 months). Each treatment cycle consisted of 28 days. During the treatment period, eligible patients received abiraterone acetate 1000 mg (administered as mg tablets) orally, once daily, and prednisolone 5 mg orally, twice daily. Patients continued to receive abiraterone until disease progression or unacceptable toxicity. Up to two dose reductions were allowed for abiraterone. However, the dose of prednisolone remained unchanged. Efficacy The primary efficacy end-point was PSA response rate (defined as proportion of patients achieving a PSA decline of 50%, according to the PSAWG criteria). Secondary end-points included overall survival (defined as the time interval from the date of the first dose of abiraterone acetate, until the date of death due to any cause); time to PSA progression (defined as the time interval from the first dose of abiraterone to the date of PSA progression as defined by the PSAWG criteria); ORR in patients with measurable disease at baseline, based on modified RECIST version 1.0 criteria; serum testosterone, and DHEA-S levels The Japanese Urological Association

3 Abiraterone in metastatic prostate cancer Safety Safety assessments included monitoring for TEAE, clinical laboratory tests, vital signs, 12-lead ECG and physical examinations. Statistical analysis The PSA response rate and its 95% CI were calculated based on the treated population (all patients who received 1 dose of abiraterone). Patients without any baseline and post-treatment measurements were considered as non-responders. The targeted PSA response rate was 30%, and the PSA response rate under the null hypothesis of no interest was 15%. With 80 patients in the study, the study had 86% power with a two-sided type I error rate of 0.05 to detect improvement in PSA response rate using an exact binomial test; this was considering that the true PSA response rate is 30% in patients treated with abiraterone plus prednisolone versus 15% in patients treated with prednisolone alone (historical control). The distribution for time-to-event variables (overall survival and time to PSA progression) was estimated using the Kaplan Meier product-limit method. The exact 95% CI was also provided for the ORR. Safety was analyzed descriptively. All statistical analyses were carried out using SAS version 9.2 (SAS Institute, Cary, NC, USA). Results Patient disposition and baseline characteristics Overall, 82 patients (52 Korean and 30 Taiwanese) were enrolled from August 2011 to January The median age of all patients was 71 years; the median PSA levels at the time of enrolment was ng/ml. A total of 79 patients (96.0%) had metastasis to bone, 39 patients (48.0%) had nodal involvement, 18 patients (22.0%) had a prostate mass (Table 1) and 74% had a Gleason score of 8. The median baseline PSA at diagnosis was higher in the Taiwanese patients ( ng/ ml; range ng/ml) compared with the Korean patients ( ng/ml; range ng/ml). All patients in the Taiwanese group had M1 disease at diagnosis; in the Korean population, 33.0% of patients had M0 disease, 62.0% had M1 disease. Proportionally more patients from Taiwan had an ECOG performance status score of 2 at baseline compared with patients from Korea (27.0% vs 14.0%, respectively). All patients received prior docetaxel therapy. The majority (82.0%) of patients had 1 line of prior docetaxel chemotherapy. Overall, 78.0% patients were treated with gonadotropin-releasing hormone analogs, and 22.0% had orchidectomy. At clinical cut-off (4 months after the last patient s first dose), 41 patients (50.0%) had discontinued the study, with disease progression (17.1%) as the most common reason for treatment discontinuation followed by withdrawal of consent (12.2%). The median treatment duration was 5.7 months (range months). During the study, one patient from Korea had single dose reduction of abiraterone because of an AE, whereas two patients from Taiwan had 2 dose reductions of abiraterone (AE: n = 1; other reasons: n = 1). Overall, 14 patients (17.1%) missed one dose of abiraterone (Korea: n = 9 [17.3%]; Taiwan: n = 5 [16.7%]), whereas 11 patients (13.4%) missed 2 doses of abiraterone (Korea: n = 10 [19.2%]; Taiwan: n = 1 [3.3%]). Of these, nine patients (36.0%) missed their dose because of AE (Korea: n = 8 [42.1%]; Taiwan: n = 1 [16.7%]) and four patients (16.0%) missed their dose because of SAE (Korea: n = 3 [15.8%]; Taiwan: n = 1 [16.7%]). Efficacy Primary end-point Overall, 35 (42.7%) patients achieved a PSA response (95% CI ), which met the primary objective of the study. Secondary end-points There were 21 (25.6%) deaths (three during the study and 18 during the survival follow-up period) at the time of data cut-off, and the 6-month event-free rate was 82.0%. Median overall survival was 11.8 months (95% CI 10.1, not estimable; Fig. 1). The median follow-up time for survival was 8.3 months (95% CI ). A total of 44 patients (53.7%) experienced PSA progression. The median time to PSA progression was 4.7 months (95% CI ) (Fig. 2). Two (4.0%) out of 50 patients evaluable for radiographic response per modified RECIST achieved partial response, while none achieved complete response (Table 2). The median testosterone concentration (1.21 nmol/l) was within the castration range (<2 nmol/l) throughout the treatment period, and the median DHEA-S decreased from μmol/l (baseline) to μmol/l (cycle 4). Safety Overall, 77 patients (94.0%) had 1 AE, 26 patients (32.0%) reported SAE, five patients (6.0%) had AE leading to study discontinuation and there was one patient with fatal AE (pleural effusion related to infectious pneumonia and disease progression). Seven deaths were reported within 30 days of the last dose of study medication (six patients died as a result of disease progression and one patient died as a result of an AE [septic shock]). The most common AE observed was bone pain (20.0%) related to bone metastases of prostate cancer, followed by hypokalemia (16.0%) and back pain (13.0%; Table 3). Most of these AE were grade 1 or 2 in severity. Overall, 27 patients (33.0%) experienced grade 3 AE, and three patients (4.0%) experienced grade 4 AE. There were no deaths due to SAE of hepatotoxicity. A total of seven patients (8.3%; n = 4, grade 3; n = 3, grade 1 or 2) experienced an AE of hypertransaminesemia. Out of the four patients with grade 3 hypertransaminesemia, two recovered after a dose reduction of abiraterone (without event recurrence), and the other two patients did not recover as a result of liver metastasis and disease progression. Grade 3 or 4 AE of special interest included hypokalemia (7.0%), fluid retention and liver function abnormalities (5.0% each), hypertension (2.0%), and cardiac disorders (1.0%). Four patients had QTcF prolongation of >30 ms; no patient had a change from baseline in QTcF prolongation of >60 ms. Postbaseline QTcF values of >450 ms were reported in 15 patients (21.0%), >480 ms in four patients 2014 The Japanese Urological Association 1241

4 CKWAKET AL. Table 1 Demographic and baseline characteristics (all treated patient population) Korea Taiwan Combined n =52 n =30 n =82 Age (years) Mean (SD) 72 (7.60) 70 (6.91) 71 (7.35) <65, n (%) 7 (14) 7 (23) 14 (17) 65 69, n (%) 16 (31) 9 (30) 25 (31) 70 74, n (%) 10 (19) 6 (20) 16 (20) 75, n (%) 19 (37) 8 (27) 27 (32) Race, n (%) Asian 52 (100) 30 (100) 82 (100) Weight (kg) Mean (SD) 65.1 (9.30) 68.2 (11.33) 66.2 (10.14) Time from initial diagnosis to 1st dose (years) Mean (SD) 4.7 (3.04) 4.5 (3.57) 4.7 (3.22) Time from staging to 1st dose (years) Mean (SD) 2.1 (2.94) 3.5 (3.29) 2.6 (3.13) Baseline PSA (ng/ml) Median (range) (0.93; ) (8.11; ) (0.93; ) Gleason score at initial diagnosis, n (%) <7 4 (8) 1 (3) 5 (6) 7 6 (12) 6 (20) 12 (14) 8 40 (77) 21 (70) 61 (74) Unknown cases 2 (4) 2 (7) 4 (6) Baseline extent of disease, n (%) Bone 50 (96) 29 (97) 79 (96) Node 22 (42) 17 (57) 39 (48) Prostate mass 10 (19) 8 (27) 18 (22) Lungs 9 (17) 6 (20) 15 (18) Liver 5 (10) 4 (13) 9 (11) Viscera 2 (4) 1 (3) 3 (4) Soft tissue 1 (2) 1 (3) 2 (2) Other viscera 1 (2) 1 (3) 2 (2) Other 2 (4) 0 2 (2) Prior cancer-related surgery, n (%) Orchiectomy 7 (14) 10 (33) 17 (21) Prostatectomy 12 (23) 4 (13) 16 (20) TURP 6 (12) 6 (20) 12 (15) Other 4 (8) 0 4 (5) ECOG performance status, n (%) 0 26 (50) 16 (53) 42 (51) 1 19 (37) 6 (20) 25 (31) 2 7 (14) 8 (27) 15 (18) Evidence of disease progression, n (%) PSA only 32 (62) 27 (90) 59 (72) Radiographic progression 20 (39) 3 (10) 23 (28) Survival (%) Time to death (months) Subjects at risk Fig. 1 Kaplan Meier curve of overall survival (all treated patient population)., Abiraterone acetate. (6.0%) and >500 ms in two patients (3.0%). No SAE of QTc prolongation was reported during the study. Discussion The current study showed that abiraterone acetate plus prednisolone effectively achieved a PSA response rate ( 50% decrease) in 43.0% of Korean and Taiwanese patients with mcrpc and previously treated with docetaxel-based chemotherapy. This is comparable with a phase II study with a similar study design carried out in the USA and UK, 13 and a phase III global study; 11 the proportion of patients with a confirmed PSA response in those studies was 36.0% and 30.0%, respectively. The 43% PSA response rate seen was despite the fact that the present study was carried out in relatively fewer patients and The Japanese Urological Association

5 Abiraterone in metastatic prostate cancer PSA progression free (%) Time to PSA progression (months) Subjects at risk Fig. 2 Kaplan Meier curve of time to PSA progression (all treated patient population). +, Censored observation; time to PSA progression is defined as the time from date of first dose until first PSA progression., Abiraterone acetate. Table 2 Best overall response (radiographic response-evaluable patient population) Korea n =28 Taiwan n =22 n (%) n (%) n (%) Combined n =50 Objective radiographic response 0 2 (9) 2 (4) Complete response Partial response 0 2 (9) 2 (4) Stable disease 22 (79) 11 (50) 33 (66) Progressive disease 6 (21) 9 (41) 15 (30) Radiographic response-evaluable patient population is defined as patients who received at least one dose of the study treatment, and had baseline and at least one post-treatment tumor assessment. had a shorter follow-up duration period compared with the global study. 11 The study met the prespecified target response rate, and supports the hypothesis that the biosynthesis of steroid hormones downstream of CYP17 contributes to progression of castration-resistant prostate cancer in Asian men. The present Asia-specific study showed that blocking androgen synthesis by inhibiting CYP17 can produce tumor responses in patients who no longer respond to standard hormonal therapies, and who had received docetaxel-based chemotherapy. It should be noted that the present study included more patients with at least one prior docetaxel therapy compared with the global study which might have led to a better PSA response. 8 The patients recruited in the present study had many poor prognostic features. Approximately 74% (77% Korean, 70% Taiwanese) of the patients enrolled had a Gleason score 8 at the time of diagnosis, in contrast to 51% in the COU-AA-301 study. 11 The extent of disease diagnosed was also considerably higher in Korean and Taiwanese patients (76% of the patients had M1 disease) compared with the extent of disease in the global study. 11 Despite these differences, the PSA response was found to be robust between these two populations, and also similar to the global findings. Furthermore, although there was no difference in overall survival, the time to PSA progression was relatively shorter. This might be attributed to the fact that sensitivity of prostate cancer to hormonal therapy and susceptibility to AE could differ among ethnic groups. An earlier Table 3 Treatment-emergent adverse events reported in at least 10% of patients (all treated patient population) Korea n =52 Taiwan n =30 n (%) n (%) n (%) Combined n =82 Total no. patients with TEAE 49 (94) 28 (93) 77 (94) Bone pain 10 (19) 6 (20) 16 (20) Hypokalemia 6 (12) 7 (23) 13 (16) Cardiac disorders 3 (6) 8 (27) 11 (13) Back pain 9 (17) 2 (7) 11 (13) Constipation 6 (12) 4 (13) 10 (12) Fatigue 5 (10) 5 (17) 10 (12) Hypertension 3 (6) 7 (23) 10 (12) Injury, poisoning and procedural 7 (14) 2 (7) 9 (11) complications Pain in extremity 7 (14) 1 (3) 8 (10) Blood alkaline phosphatase increased 0 8 (27) 8 (10) Anemia 4 (8) 4 (13) 8 (10) Aspartate aminotransferase increased 1 (2) 6 (20) 7 (9) Insomnia 1 (2) 6 (20) 7 (9) Edema peripheral 2 (4) 5 (17) 7 (9) Decreased appetite 3 (6) 4 (13) 7 (9) Upper respiratory tract infection 2 (4) 5 (17) 7 (9) Vomiting 1 (2) 5 (17) 6 (7) Nasopharyngitis 3 (6) 3 (10) 6 (7) Cough 1 (2) 5 (17) 6 (7) Hematuria 3 (6) 3 (10) 6 (7) Abdominal discomfort 2 (4) 4 (13) 6 (7) Dyspepsia 6 (12) 0 6 (7) Abdominal distension 1 (2) 4 (13) 5 (6) Arthralgia 0 5 (17) 5 (6) Muscular weakness 1 (2) 4 (13) 5 (6) Alanine aminotransferase increased 1 (2) 4 (13) 5 (6) Nocturia 1 (2) 3 (10) 4 (5) Proteinuria 1 (2) 3 (10) 4 (5) Hyperglycemia 0 4 (13) 4 (5) Hypoesthesia 1 (2) 3 (10) 4 (5) Ecchymosis 0 3 (10) 3 (4) study comparing the efficacy of hormonal therapy between Japanese Americans and Caucasians living in Hawaii showed that despite similar backgrounds of both groups, overall and cause-specific survival rates of Japanese Americans were better than those of Caucasian patients. 18 The safety profile of abiraterone in Korean and Taiwanese patients is consistent with the established safety profile of abiraterone in global phase III studies. 7,15 Consistent with the results seen in the COU-AA-301 study, the primary reason for discontinuation of abiraterone treatment was progressive disease, and not toxicity. 15 As expected, the most frequently reported AE were based on the underlying disease characteristics of these patients, and were consistent with AE reported in other abiraterone mcrpc clinical studies. 7,11,15 Mineralocorticoid-related toxicities were predominately grade 1 or 2 in severity. No discontinuations as a result of hypertension, hypokalemia or peripheral edema were reported. Increases in alkaline phosphatase were reported in eight patients (10%; grade 3: four [5%]; grade 4: one [1%]); however, these results are difficult to interpret, as most of the patients had bone metastases, which frequently lead to high 2014 The Japanese Urological Association 1243

6 CKWAKET AL. concentrations of alkaline phosphatase, mainly from the bone alkaline phosphatase isoenzyme. There were no SAE or discontinuations as a result of hepatotoxicity. All liver function test abnormalities for patients without progression of liver metastases were resolved after dose reduction or interruption of abiraterone. However, the median treatment duration of the present study was much shorter than that of the global study, and hence, further long-term studies are warranted to confirm the safety profile of abiraterone in the Asian population. 11 The present study showed that abiraterone plus prednisolone effectively achieved PSA response rate in 43% of Asian patients with mcrpc, after failed docetaxel-based chemotherapy, and provided additional evidence that selective CYP17 inhibition with abiraterone acetate in Asians is well tolerated and has significant antitumor activity. These results highlight the continued importance of the AR axis in Asians, similar to Caucasians. This clinical effectiveness of abiraterone in treating mcrpc in these patients without completely inhibiting the action of testosterone AR further implies that, in future, there is a scope to establish more powerful first-line androgen deprivation therapy in the Asian population. Acknowledgments The authors thank Dr Susan Li, previously at Janssen R&D, for data analysis; Dr Shruti Shah (SIRO Clinpharm Pvt. Ltd) for providing writing assistance and Dr Namit Ghildyal (Janssen R&D, LLC.) for providing additional editorial support for this manuscript. The authors thank all the patients for their participation in this study, and acknowledge the collaboration and commitment of all investigators and their staff. Conflict of interest None declared. References 1 Pu YS, Chiang HS, Lin CC, Huang CY, Huang KH, Chen J. Changing trends of prostate cancer in Asia. Aging Male 2004; 7: Bureau of Health Promotion, Department of Health, The Executive Yuan Taiwan. Cancer Registry Annual Report, 2009 Taiwan, published February Taiwan Cooperative Oncology Group (TCOG), National Health Research Institutes [NHRI]. Taiwan Prostate Cancer Guideline, 3rd edn. October Jung KW, Won YJ, Kong HJ, Oh CM, Seo HG, Lee JS. Cancer statistics in Korea: incidence, mortality, survival and prevalence in Cancer Res. Treat. 2013; 45: Jung KW, Won YJ, Kong HJ, Oh CM, Shin A, Lee JS. Survival of korean adult cancer patients by stage at diagnosis, : national cancer registry study. Cancer Res. Treat. 2013; 45: Attard G, Reid AH, A Hern R et al. Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J. Clin. Oncol. 2009; 27: Danila DC, Morris MJ, de Bono JS et al. Phase II multicenter study of abiraterone acetate plus prednisone therapy in patients with docetaxel-treated castration-resistant prostate cancer. J. Clin. Oncol. 2010; 28: Tolcher AW, Cooper J. Castration-resistant prostate cancer hormone therapy redux. J. Clin. Oncol. 2010; 28: O Donnell A, Judson I, Dowsett M et al. Hormonal impact of the 17alpha-hydroxylase/C(17,20)-lyase inhibitor abiraterone acetate (CB7630) in patients with prostate cancer. Br. J. Cancer 2004; 90: Barrie SE, Potter GA, Goddard PM, Haynes BP, Dowsett M, Jarman M. Pharmacology of novel steroidal inhibitors of cytochrome P450(17) alpha (17 alpha-hydroxylase/c17-20 lyase). J. Steroid Biochem. Mol. Biol. 1994; 50: de Bono JS, Logothetis CJ, Molina A et al. Abiraterone and increased survival in metastatic prostate cancer. N. Engl. J. Med. 2011; 364: Attard G, Swennenhuis JF, Olmos D et al. Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer. Cancer Res. 2009; 69: Reid AH, Attard G, Danila DC et al. Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate. J. Clin. Oncol. 2010; 28: Ryan CJ, Smith MR, Fong L et al. Phase I clinical trial of the CYP17 inhibitor abiraterone acetate demonstrating clinical activity in patients with castration-resistant prostate cancer who received prior ketoconazole therapy. J. Clin. Oncol. 2010; 28: Fizazi K, Scher HI, Molina A et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012; 13: Bubley GJ, Carducci M, Dahut W et al. Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group. J. Clin. Oncol. 1999; 17: Eisenberger MA, Blumenstein BA, Crawford ED et al. Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. N. Engl. J. Med. 1998; 339: Namiki M, Ueno S, Kitagawa Y, Fukagai T, Akaza H. Effectiveness and adverse effects of hormonal therapy for prostate cancer: Japanese experience and perspective. Asian J. Androl. 2012; 14: The Japanese Urological Association