Abiraterone acetate in metastatic castration-resistant prostate cancer - the unanticipated real-world clinical experience.

BACKGROUND: There is much interest in confirming whether the efficacy of abiraterone acetate (AA) demonstrated within the trial setting is reproducible in routine clinical practice. We report the clinical outcome of metastatic castration-resistant prostate cancer (mCRPC) patients treated with AA in real-life clinical practice. METHODS: The clinical records of mCRPC patients treated with AA from all 6 public oncology centers in Hong Kong between August 2011 and December 2014 were reviewed. The treatment efficacy and its determinants, and toxicities were determined. RESULTS: A total of 110 patients with mCRPC were treated with AA in the review period, of whom 58 were chemo-naive and 52 had received prior chemotherapy (post-chemo). The median follow-up time was 7.5/11.4 months for chemo-naive/post-chemo patients. 6.9/15.4 % of chemo-naive/post-chemo patients had visceral metastases. The median overall survival (OS) and progression-free survival (PFS) were 18.1/15.5 months and 6.7/6.4 months for chemo-naive/post-chemo patients, respectively. Among chemo-naive patients, those with visceral diseases had significantly inferior OS (2.8 vs 18.0 p = 0.0007) and PFS (2.8 vs 6.8 months, p = 0.0088) than those without. Pain control was comparable in both groups of patients. The most common grade 3 or above toxicities were hypertension (6.9/5.8 %) and hypokalemia (3.4/3.8 %) in chemo-naive/post-chemo patients. In multivariate analysis, the presence of prostate-specific antigen (PSA) response (≥50 % drop of PSA from baseline) within the first 3 months of therapy was associated with favorable OS and PFS in both chemo-naive and post-chemo group. CONCLUSIONS: In clinical practice outside the trial setting, OS after AA in our chemo-naive patient cohort (18.1 months) was considerably shorter than that reported in the COU-AA-302 trial (34.7 months), and the OS was particularly short in those with visceral metastases (2.8 months). Conversely, AA was efficacious in post-chemo patients. AA resulted in comparable pain control in both groups of patients. The presence of PSA response within the first 3 months of treatment was a significant determinant of survival.

Genetic Testing and Its Clinical Application in Prostate Cancer Management: Consensus Statements from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology.

Background: In recent years, indications for genetic testing in prostate cancer (PC) have expanded from patients with a family history of prostate and/or related cancers to those with advanced castration-resistant disease, and even to early PC patients for determination of the appropriateness of active surveillance. The current consensus aims to provide guidance to urologists, oncologists and pathologists working with Asian PC patients on who and what to test for in selected populations. Methods: A joint consensus panel from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology was convened over a series of 5 physical and virtual meetings. A background literature search on genetic testing in PC was performed in PubMed, ClinicalKey, EBSCOHost, Ovid and ProQuest, and three working subgroups were formed to review and present the relevant evidence. Meeting agendas adopted a modified Delphi approach to ensure that discussions proceed in a structured, iterative and balanced manner, which was followed by an anonymous voting on candidate statements. Of 5 available answer options, a consensus statement was accepted if ≥ 75% of the panelists chose "Accept Completely" (Option A) or "Accept with Some Reservation" (Option B). Results: The consensus was structured into three parts: indications for testing, testing methods, and therapeutic implications. A list of 35 candidate statements were developed, of which 31 were accepted. The statements addressed questions on the application of PC genetic testing data and guidelines to Asian patients, including patient selection for germline testing, selection of gene panel and tissue sample, provision of genetic counseling, and use of novel systemic treatments in metastatic castration-resistant PC patients. Conclusion: This consensus provides guidance to urologists, oncologists and pathologists working with Asian patients on indications for genetic testing, testing methods and technical considerations, and associated therapeutic implications.

Ethnic Pharmacogenomic Differences in the Management of Asian Patients with Metastatic Prostate Cancer.

Progression to metastatic disease occurs in about half of all men who develop prostate cancer (PC), one of the most common cancers in men worldwide. Androgen deprivation therapy has been the mainstay therapy for patients with metastatic PC (mPC) since the 1940s. In the last decade, there has been unprecedented advancement in systemic therapies, e.g., taxane, androgen-signalling pathway inhibitors, and biomarker-driven targeted therapies for various stages of disease, resulting in overall survival improvement. Adding to ongoing controversies over how best to treat these patients is the recognition that ethnicity may influence prognosis and outcomes. This review discusses recent evidence for the impacts of Asian ethnicity specifically, which includes environmental, sociocultural, and genetic factors, on the approach to pharmacological management of mPC. Clear inter-ethnic differences in drug tolerability, serious adverse events (AEs), and genetic heterogeneity must all be considered when dosing and scheduling for treatment, as well as designing future precision studies in PC.

A Territory-wide, Multicenter, Age- and Prostate-specific Antigen-matched Study Comparing Chemohormonal Therapy and Hormonal Therapy Alone in Chinese Men With Metastatic Hormone-sensitive Prostate Cancer.

BACKGROUND: There is a lack of real-world data regarding the treatment outcomes of chemohormonal therapy versus hormonal therapy alone in Chinese men with metastatic hormone-sensitive prostate cancer. PATIENTS AND METHODS: We conducted a territory-wide, multicenter, age- and prostate-specific antigen (PSA)-matched cohort study comparing chemohormonal therapy and hormonal therapy alone in Chinese men with metastatic hormone-sensitive prostate cancer. Patient and disease characteristics were reviewed. The primary outcome was PSA progression-free survival. Secondary outcomes included clinical progression-free survival and castration resistance-free survival. Kaplan-Meier and multivariate Cox regression analyses were performed. RESULTS: From January 2015 to July 2016, 32 Chinese men with metastatic hormone-sensitive prostate cancer were treated with chemohormonal therapy, and they were matched to 32 Chinese men who were treated with hormonal therapy alone. Patient and disease characteristics were similar between the 2 groups. The chemohormonal therapy group had a significantly better PSA progression-free survival (P = .001) and castration resistance-free survival (P = .002) than the hormonal therapy group. There was no significant difference in the clinical progression-free survival between the 2 groups. Upon multivariate Cox regression analyses, the use of chemohormonal therapy was significantly associated with a longer time to PSA progression (hazard ratio, 0.31; 95% confidence interval, 0.31-0.73; P = .008) and a longer time to castration resistance (hazard ratio, 0.38; 95% confidence interval, 0.17-0.83; P = .015), but was not associated with clinical progression. CONCLUSIONS: The use of chemohormonal therapy could prevent PSA progression and the development of castration resistance when compared with hormonal therapy alone in Chinese men with metastatic hormone-sensitive prostatic cancer.

Preliminary efficacy and tolerability of chemohormonal therapy in metastatic hormone-naïve prostate cancer: The first real-life experience in Asia.

INTRODUCTION: A substantial survival benefit with chemohormonal therapy has been proven by the CHAARTED and STAMPEDE studies, and this clinical approach has emerged as the standard of care for patients with metastatic hormone-naïve prostate cancer (mHSPC). However, because its clinical efficacy and tolerability in Asian patients remains uncertain, this study aims to evaluate preliminary results of its use in Hong Kong. METHODS: The clinical records of mHSPC patients treated with chemohormonal therapy from all six public oncology centers in Hong Kong between January 2015 and July 2016 were reviewed. Time to castration-resistant prostate cancer (CRPC), treatment-related complications, prostate-specific antigen (PSA) response and the time to PSA nadir were assessed. RESULTS: A total of 32 patients (median age, 66 years) were treated with chemohormonal therapy in the review period. After median follow-up time of 11.4 months, the median time to CRPC and time to PSA nadir were 19.5 months and 7 months, respectively. PSA response (>50% drop in PSA level from baseline) was achieved in all patients and the median maximal PSA response was 99.6%. The rates of grade 3 or 4 febrile neutropenia, neutropenia and anemia were 12.5%, 40.6% and 3.1%, respectively. CONCLUSION: Early efficacy with chemohormonal therapy in Asian mHSPC patients was comparable to the pivotal study and biochemical response is promising. The high frequency of hematologic toxicities in Asian patients highlights the importance of proper patient selection and pre-emptive use of granulocyte colony-stimulating factor.

Differences in clinical outcome between docetaxel and abiraterone acetate as the first-line treatment in chemo-naïve metastatic castration-resistant prostate cancer patients with or without the ineligible clinical factors of the COU-AA-302 study.

BACKGROUND: This study aimed to compare the efficacy of abiraterone acetate (AA) versus docetaxel (T) as first-line treatment in chemo-naïve metastatic castration-resistant prostate cancer (mCRPC) patients with or without the ineligible factors of the COU-AA-302 study (presence of visceral metastases, symptomatic disease, and/or Eastern Cooperative Oncology Group performance status ≥ 2). MATERIALS AND METHODS: The clinical records of chemo-naïve mCRPC patients who received AA in six public oncology centers or T in two of these centers between 2003 and 2014 were reviewed. The survival time was compared among four subgroups of patients: those with ineligible factors administered AA (Group Ineligible-AA) or T (Group Ineligible-T), and those without ineligible factors and administered AA (Group Eligible-AA) or T (Group Eligible-T). RESULTS: During the study period, we identified 115 mCRPC patients who received AA or T, among whom 29, 36, 29, and 21 patients were classified as Groups Ineligible-AA, Ineligible-T, Eligible-AA, and Eligible-T, respectively. Both Group Ineligible-AA and Group Eligible-AA had significantly longer progression-free survival (PFS) and similar overall survival (OS) as Group Ineligible-T and Group Eligible-T (Ineligible, PFS: 6.3 vs. 5.9 months, P = 0.0234, OS: 7.8 vs. 15.7 months, P = 0.1601; Eligible, PFS: 9.8 vs. 5.6 months, P = 0.0437, OS: 20.5 vs. 18.2 months, P = 0.7820). CONCLUSIONS: Compared to T, AA treatment resulted in longer PFS and similar OS in chemo-naïve mCRPC patients, irrespective of the presence of ineligible factors, suggesting that the initial treatment by AA may still be beneficial to those with the aforementioned ineligible factors.

Survival Outcomes, Prostate-specific Antigen Response, and Tolerance in First and Later Lines of Enzalutamide Treatment for Metastatic Castration-resistant Prostate Cancer: A Real-World Experience in Hong Kong.

BACKGROUND: The present study retrospectively evaluated the efficacy and safety of enzalutamide in different lines of metastatic castration-resistant prostate cancer (mCRPC) treatment in a real-world setting. PATIENTS AND METHODS: The clinical records of patients with mCRPC treated with enzalutamide between August 2015 and October 2017 were retrieved from all 7 public oncology centers in Hong Kong and reviewed. The primary endpoint was progression-free survival (PFS) in first (1L), second (2L), and third or fourth lines (3L or 4L) of CRPC treatment. Secondary endpoints included overall survival (OS), prostate-specific antigen (PSA) response, and tolerance. RESULTS: Among a total of 117 patients (median age of 73 years [range, 52-90 years]), 34 (29.1%), 57 (48.7%), and 26 (19.3%) patients had enzalutamide as their 1L (chemo-naive), 2L (post-docetaxel or -abiraterone), and 3L or above treatment options. The overall PSA response rates were 43.6%, and were 73.5%, 35.1%, and 19.2% for 1L, 2L, and 3L or 4L treatment, respectively. PFS and OS were significantly associated with the line of treatment in the univariate survival analysis (1L/2L/3L and 4L; PFS, 7.1/3.9/2.2 months; OS, not reached/15.8/7.4 months; both P = .0002) but not in the multivariate analysis. The observed incidence of any fatigue (grade 1 or 2, 54.7%; grade 3 or 4, 9.4%) was much higher than reported in the AFFIRM (A Study Evaluating the Efficacy and Safety of the Investigational Drug MDV3100 [ClinicalTrials.gov Identifier: NCT00974311]) (any grade, 34%) and PREVAIL (A Multinational Phase 3, Randomized, Double-blind, Placebo-controlled Efficacy And Safety Study Of Oral Mdv3100 In Chemotherapy-naïve Patients With Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy [ClinicalTrials.gov Identifier: NCT00974311]) (any grade, 36%) trials; as well, grade ≥ 2 fatigue was significantly associated with 3L or 4L treatment (P = .01 in both univariate and multivariate analyses). CONCLUSION: In the real-life setting, there was a higher incidence of enzalutamide-related fatigue than reported in the trials. Earlier lines of enzalutamide treatment were associated with longer PFS and OS, more frequent PSA response, and less fatigue.