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Background and Purpose: There is growing concern about the adverse metabolic and cardiovascular effects of abiraterone acetate (AA) and enzalutamide (ENZ), two standard hormonal therapies for prostate cancer. We analysed the risk of cardiovascular adverse events among patients treated with AA and ENZ., Patients and Methods: We used Kythera Medicare data from January 2019 to June 2023 to identify patients with at least one pharmacy claim for AA or ENZ. The index date was the first prescription claim date. Patients were required to have 1 year of data pre- and post-index date. New users excluded those with prior AA or ENZ claims and pre-existing cardiovascular comorbidities. Demographic and clinical variables, including age, socioeconomic status (SES), comorbidity score, prostate-specific comorbidities, and healthcare costs, were analysed . Propensity score matching was employed for risk adjustment., Results: Of the 8,929 and 8,624 patients in the AA and ENZ cohorts, respectively, 7,647 were matched after adjusting for age, sociodemographic, and clinical factors. Between the matched cohorts (15.54% vs. 14.83%, p < 0.05), there were no statistically significant differences in any cardiovascular event after adjusting for these factors. The most common cardiovascular event in both cohorts was heart failure (5.20% vs. 4.49%), followed by atrial fibrillation (4.42% vs. 3.60%) and hypotension (2.93% vs. 2.48%)., Interpretation: This study provides real-world evidence of the cardiovascular risk of AA and ENZ that may not appear in clinical trial settings. Adjusting for age, baseline comorbidities, and SES, the likelihood of a cardiovascular event did not differ between treatment groups.

Importance: The association between the use of bone-modifying agents (BMAs) and the outcomes among patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with abiraterone acetate plus prednisone (AAP) remains unclear., Objective: To investigate the association between BMA use and the outcomes of patients with mCSPC receiving AAP., Design, Setting, and Participants: In this cohort study, a post hoc analysis of individual participant data from the LATITUDE trial was performed. The LATITUDE trial, a phase 3 randomized clinical trial, aimed to assess the efficacy of AAP and androgen deprivation therapy (ADT) vs dual-placebo and ADT in patients with high-risk mCSPC (data cutoff, August 15, 2018). Eligible patients had newly diagnosed prostate cancer with metastases and at least 2 of 3 high-risk factors (Gleason score ≥8, presence of ≥3 lesions on bone scan, or presence of measurable visceral metastasis). The trial was conducted at 235 sites in 34 countries. Data for the present study were evaluated from July 18 to September 23, 2023., Exposures: Use of BMAs was defined as the administration of bisphosphonates and denosumab within 90 days before and after randomization., Main Outcomes and Measures: The primary outcomes were time to skeletal-related events (SREs) and overall survival (OS). An SRE was defined as a clinical or pathological fracture, spinal cord compression, palliative radiation to bone, or surgery involving bone. Differences in these outcomes were examined using the restricted mean survival time from inverse probability of treatment weighting-adjusted Kaplan-Meier curves, estimated until the last event was observed (longest time observed, 63.9 months). Treatment × covariate interactions were analyzed using weighted Cox proportional hazards regression models for the total cohort., Results: In the total cohort of 1199 patients (956 [79.7%] younger than 75 years), 597 (49.8%) received AAP and ADT, including 474 (79.4%) younger than 75 years and 384 (64.3%) with more than 10 bone metastases (AAP cohort); 602 (50.2%) were treated with dual placebo and ADT, including 482 (80.1%) younger than 75 years and 377 (62.6%) with more than 10 bone metastases (ADT cohort). In the AAP cohort, 132 patients (22.1%) received BMAs, while in the ADT cohort, 131 (21.8%) did. Zoledronic acid was the most frequently administered BMA in both the AAP (93 [70.5%]) and the ADT (88 [67.2%]) cohorts. During the median follow-up of 51.8 (IQR, 47.2-57.0) months in the AAP cohort, BMA use was associated with a longer time to SRE (difference, 7.8 [95% CI, 4.2-11.3] months) but not with OS (difference, 1.6 [95% CI, -2.5 to 5.8] months). In the ADT cohort, BMA use was associated with both time to SRE (difference, 9.3 [95% CI, 5.2-13.3] months) and OS (difference, 5.5 [95% CI, 3.2-9.8] months). No evidence was found that the outcomes of BMA varied by AAP or ADT (hazard ratio for time to SRE, 0.99 [95% CI, 0.48-2.08]; P = .99 for interaction; hazard ratio for OS, 1.31 [95% CI, 0.88-1.96]; P = .18 for interaction)., Conclusions and Relevance: The findings of this cohort study suggest that use of BMAs was associated with a longer time to SRE in patients with high-risk mCSPC treated with ADT, with or without AAP, suggesting that BMA use might provide benefits to this population.

Purpose: Early treatment intensification with neoadjuvant therapy may improve outcomes in patients with high-risk, localized prostate cancer treated with radical prostatectomy. Our objective was to compare pathologic, oncologic, and safety outcomes of neoadjuvant abiraterone acetate plus leuprolide acetate with or without cabazitaxel prior to radical prostatectomy in patients with localized, high-risk prostate cancer., Patients and Methods: This open-label, multicenter, phase II trial randomized men with clinically localized, D'Amico high-risk prostate cancer to neoadjuvant abiraterone acetate (1,000 mg/day) and leuprolide acetate (22.5 mg every 3 months) with or without cabazitaxel (25 mg/m2) prior to radical prostatectomy. The primary outcome was pathologic complete response (pCR) or minimal residual disease (MRD). Secondary outcomes included surgical margins, lymph node involvement, pathologic stage, 12-month biochemical relapse-free survival (BRFS) rates, and safety profile., Results: The per-protocol population consisted of 70 patients [cabazitaxel arm (Arm A): 37, no cabazitaxel arm (Arm B): 33]. Median patient age and prostate-specific antigen levels were 63.5 years [interquartile range (IQR), 58.0-68.0] and 21.9 ng/mL (IQR, 14.6-42.8), respectively. pCR/MRD occurred in 16 (43.2%) versus 15 patients (45.5%) in arms A and B, respectively (P = 0.85). pCR occurred in two (5.4%) versus three patients (9.1%) in arms A and B, respectively (P = 0.66). Patients with ≤ 25% total biopsy cores positive had increased odds of pCR/MRD (P = 0.04). Patients with pCR/MRD had superior 12-month BRFS rates (96.0% vs. 62.0%, P = 0.03). Grade 3+ adverse events occurred in 42.5% and 23.7% of patients in arms A and B, respectively (P = 0.078)., Conclusions: Neoadjuvant cabazitaxel addition to abiraterone acetate/leuprolide acetate prior to radical prostatectomy did not improve pCR/MRD in clinically localized, high-risk prostate cancer., (©2023 American Association for Cancer Research.)

Background: This research work was aimed at evaluating the incidence and risk factors of adverse events (AEs) occurring in patients treated with abiraterone acetate (AA) and prednisone (PDN) outside clinical trials. These associations were assessed regarding the survival outcomes., Methods: The study included 191 patients aged ≥18 years of confirmed metastatic castration-resistant prostate cancer (mCRPC) between March 2017 and April 2022. AE incidences were descriptively summarized from the whole cohort. Baseline characteristics, safety (treatment-emergent AEs and severe AEs), and efficacy [progression-free survival (PFS)] were analyzed. Multi-variable Cox proportional hazards models were employed to assess the factors linked with PFS., Results: Overall, the median PFS was 17.16 months (range, 0.5-57.58). Patient baseline prostate-specific antigen (PSA) ≧̸10 ng/ml ( p = 0.000), multiple organ metastasis ( p = 0.007), hypertension ( p = 0.004), and coronary heart disease ( p = 0.004) were associated with worse PFS; however, radiotherapy ( p = 0.028) was linked to better PFS at univariate analysis in the overall cohort. Baseline multiple organ metastasis, hypertension, and radiotherapy remained statistically significant in multivariable models ( p = 0.007, p = 0.005, and p = 0.011, respectively).Incidence of AEs showed increased bilirubin (BIL) (55/191 patients, 28.8%) followed by increased alanine aminotransferase/aspartate aminotransferase (ALT/AST) (48/191 patients, 25.09%). The most common grade 3 AEs were increased ALT (3/191, 1.57%) followed by elevated BIL, hypercholesterolemia, and hypokalemia. Anemia had shorter PFS. There were no unexpected AEs in any patient., Conclusion: AA is effective and tolerated in asymptomatic or slightly symptomatic mCRPC in "real-life" setting. The survival outcomes are influenced by multiple organ metastasis, hypertension, and radiotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Yan, Le, Li, Xing and Li.)

Niraparib (NIRA) is a highly selective inhibitor of poly (adenosine diphosphate-ribose) polymerase, PARP1 and PARP2, which play a role in DNA repair. The phase II QUEST study evaluated NIRA combinations in patients with metastatic castration-resistant prostate cancer who were positive for homologous recombination repair gene alterations and had progressed on 1 prior line of novel androgen receptor-targeted therapy. Results from the combination of NIRA with abiraterone acetate plus prednisone, which disrupts androgen axis signaling through inhibition of CYP17, showed promising efficacy and a manageable safety profile in this patient population., (© The Author(s) 2023. Published by Oxford University Press.)

Background: We aimed to develop and validate a plasma extracellular vesicle circular RNA (circRNA)-based signature that can predict overall survival (OS) in first-line abiraterone therapy for metastatic castration-resistant prostate cancer (mCRPC) patients., Methods: In total, 582 mCRPC patients undergoing first-line abiraterone therapy from four institutions were sorted by three phases. In the discovery phase, 30 plasma samples from 30 case-matched patients with or without early progression were obtained to generate circRNA expression profiles using RNA sequencing. In the training phase, differentially expressed circRNAs were examined using digital droplet PCR in a training cohort (n = 203). The circRNA signature was constructed using a least absolute shrinkage and selection operator Cox regression to predict OS. In the validation phase, the prognostic ability of this signature was prospectively validated in two external cohorts (Cohort I, n = 183; Cohort II, n = 166)., Results: We developed a five-circRNA signature, based on circCEP112, circFAM13A, circBRWD1, circVPS13C and circMACROD2, which successfully stratified patients into high-risk and low-risk groups. The prognostic ability of this signature was prospectively validated in two external cohorts (P < 0.0001, P < 0.0001). Patients with high-risk scores had shorter OS than patients with low-risk scores., Conclusion: This five-circRNA signature is a reliable predictor of OS for mCRPC patients undergoing abiraterone., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: Abiraterone Acetate (AA) is an important agent in the treatment of advanced prostate cancer. It was primarily approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) after failure of androgen deprivation therapy. There is still no available strong data regarding the impact of early decline of prostate-specific antigen (PSA) in the overall survival. The aim of this study was to evaluate the clinical efficacy of an early prostate-specific antigen response as a predictor of overall survival (OS) in metastatic castration-resistant prostate cancer when treated with Abiraterone Acetate., Materials and Methods: A dual center, retrospective, cohort study on patients diagnosed with mCRPC treated with abiraterone between 2013 and 2020 was performed. Primary end-point was to demonstrate the efficacy of AA, with the analysis of PSA decline, and the correlation with overall survival., Results: The cohort analysis consisted of 84 patients with a median age of 71 ± 9 years. A PSA response of > 30% and > 50% at 60 and 90 days was associated with improved OS. Multivariate analysis revealed that a 60 day PSA decline of > 30% was predictive of overall survival. Median OS of diag-nosed mCRPC patients was 28 months. Docetaxel pre-treatment was not associated with longer OS. The median duration of drug exposure for patients submitted to AA was found to be 14 months., Conclusions: Early PSA response rate can offer clinically meaningful information and can be considered a surrogate of longer OS. A > 30% or > 50% prostate-specific antigen decline at 60 and 90 days provided an important low-cost clinical tool to predict subsequent events in mCRPC patients treated with abiraterone.

We identified resistance mechanisms to abiraterone acetate/prednisone (AA/P) in patients with metastatic castration-resistant prostate cancer (mCRPC) in the Prostate Cancer Medically Optimized Genome-Enhanced Therapy (PROMOTE) study., We analyzed whole-exome sequencing (WES) and RNA-sequencing data from 83 patients with metastatic biopsies before (V1) and after 12 weeks of AA/P treatment (V2). Resistance was determined by time to treatment change (TTTC)., At V2, 18 and 11 of 58 patients had either short-term (median 3.6 months; range 1.4-4.5) or long-term (median 29 months; range 23.5-41.7) responses, respectively. Nonresponders had low expression of TGFBR3 and increased activation of the Wnt pathway, cell cycle, upregulation of AR variants, both pre- and posttreatment, with further deletion of AR inhibitor CDK11B posttreatment. Deletion of androgen processing genes, HSD17B11, CYP19A1 were observed in nonresponders posttreatment. Genes involved in cell cycle, DNA repair, Wnt-signaling, and Aurora kinase pathways were differentially expressed between the responder and non-responder at V2. Activation of Wnt signaling in nonresponder and deactivation of MYC or its target genes in responders was detected via SCN loss, somatic mutations, and transcriptomics. Upregulation of genes in the AURKA pathway are consistent with the activation of MYC regulated genes in nonresponders. Several genes in the AKT1 axis had increased mutation rate in nonresponders. We also found evidence of resistance via PDCD1 overexpression in responders., Implications: Finally, we identified candidates drugs to reverse AA/P resistance: topoisomerase inhibitors and drugs targeting the cell cycle via the MYC/AURKA/AURKB/TOP2A and/or PI3K&#95;AKT&#95;MTOR pathways., (©2022 The Authors; Published by the American Association for Cancer Research.)

Importance: Bone resorption inhibitors (BRIs) are recommended by international guidelines to prevent skeletal-related events (SREs) among patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases. Abiraterone acetate with prednisone is currently the most common first-line therapy for the treatment of patients with mCRPC; however, the clinical impact of the addition of BRIs to abiraterone acetate with prednisone in this disease setting is unknown., Objective: To evaluate the association of the use of concomitant BRIs with overall survival (OS) and time to first SRE among patients with mCRPC and bone metastases receiving abiraterone acetate with prednisone as first-line therapy., Design, Setting, and Participants: This retrospective cohort study collected data from 745 consecutive patients who began receiving abiraterone acetate with prednisone as first-line therapy for mCRPC with bone metastases between January 1, 2013, and December 31, 2016. Data were collected from 8 hospitals in Canada, Europe, and the US from June 15 to September 15, 2019., Exposures: Patients were classified by receipt vs nonreceipt of concomitant BRIs and subclassified by volume of disease (high volume or low volume, using definitions from the Chemohormonal Therapy Vs Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer [CHAARTED] E3805 study) at the initiation of abiraterone acetate with prednisone therapy., Main Outcomes and Measures: The primary end point was OS. The secondary end point was time to first SRE. The Kaplan-Meier method and Cox proportional hazards models were used., Results: Of the 745 men (median age, 77.6 years [interquartile range, 68.1-83.6 years]; 699 White individuals [93.8%]) included in the analysis, 529 men (71.0%) received abiraterone acetate with prednisone alone (abiraterone acetate cohort), and 216 men (29.0%) received abiraterone acetate with prednisone plus BRIs (BRI cohort). A total of 420 men (56.4%) had high-volume disease, and 276 men (37.0%) had low-volume disease. The median follow-up was 23.5 months (95% CI, 19.8-24.9 months). Patients in the BRI cohort experienced significantly longer OS compared with those in the abiraterone acetate cohort (31.8 vs 23.0 months; hazard ratio [HR], 0.65; 95% CI, 0.54-0.79; P < .001). The OS benefit in the BRI cohort was greater for patients with high-volume vs low-volume disease (33.6 vs 19.7 months; HR, 0.51; 95% CI, 0.38-0.68; P < .001). The BRI cohort also had a significantly shorter time to first SRE compared with the abiraterone acetate cohort (32.4 vs 42.7 months; HR, 1.27; 95% CI, 1.00-1.60; P = .04), and the risk of a first SRE was more than double in the subgroup with low-volume disease (HR, 2.29; 95% CI, 1.57-3.35; P < .001). In the multivariable analysis, concomitant BRIs use was independently associated with longer OS (HR, 0.64; 95% CI, 0.52-0.79; P < .001)., Conclusions and Relevance: In this study, the addition of BRIs to abiraterone acetate with prednisone as first-line therapy for the treatment of patients with mCRPC and bone metastases was associated with longer OS, particularly in patients with high-volume disease. These results suggest that the use of BRIs in combination with abiraterone acetate with prednisone as first-line therapy for the treatment of mCRPC with bone metastases could be beneficial.

Aim: The aim was to evaluate the efficacy and safety of abiraterone acetate plus prednisolone in patients with chemotherapy-naïve early metastatic castration-resistant prostate cancer who failed first-line androgen deprivation therapy., Methods: Patients with early metastatic castration-resistant prostate cancer with confirmed prostate-specific antigen progression within 1-year or prostate-specific antigen progression without having normal prostate-specific antigen level (<4.0 ng/mL) during first-line androgen deprivation therapy were enrolled and administered abiraterone acetate (1000 mg) plus prednisolone (10 mg). A minimum of 48 patients were required according to Simon's minimax design. The primary endpoint was prostate-specific antigen response rate (≥50% prostate-specific antigen decline by 12 weeks), secondary endpoints included prostate-specific antigen progression-free survival and overall survival. Safety parameters were also assessed., Results: For efficacy, 49/50 patients were evaluable. Median age was 73 (range: 55-86) years. The median duration of initial androgen deprivation therapy was 32.4 (range: 13.4-84.1) weeks and 48 patients experienced prostate-specific antigen progression within 1-year after initiation of androgen deprivation therapy. prostate-specific antigen response rate was 55.1% (95% confidence interval: 40.2%-69.3%), median prostate-specific antigen-progression-free survival was 24.1 weeks, and median overall survival was 102.9 weeks (95% confidence interval: 64.86 not estimable [NE]). Most common adverse event was nasopharyngitis (15/50 patients, 30.0%). The most common ≥grade 3 adverse event was alanine aminotransferase increased (6/50 patients, 12.0%)., Conclusions: Abiraterone acetate plus prednisolone demonstrated a high prostate-specific antigen response rate of 55.1%, suggesting tumor growth still depends on androgen synthesis in patients with early metastatic castration-resistant prostate cancer. However, prostate-specific antigen-progression-free survival was shorter than that reported in previous studies. Considering the benefit-risk profile, abiraterone acetate plus prednisolone would be a beneficial treatment option for patients with chemotherapy-naive metastatic prostate cancer who show early castration resistance., (© The Author(s) 2020. Published by Oxford University Press.)

Background: Systemic androgen deprivation therapy (ADT), also referred to as hormone therapy,àhas long been the primary treatment for metastatic prostate cancer. Additional agents have been reserved for the castrate-resistant disease stage when ADT start becoming less effective. Abiraterone is an agent with an established role in that disease stage, which has only recently been evaluated in the hormone-sensitive setting., Objectives: To assess the effects of early abiraterone acetate, in combination with systemic ADT, for newly diagnosed metastatic hormone-sensitive prostate cancer., Search Methods: We searched CENTRAL, MEDLINE, Embase, six other databases, two trials registries, grey literature, and conference proceedings, up to 15 May 2020. We applied no restrictions on publication language or status., Selection Criteria: We included randomized trials, in which men diagnosed with hormone-sensitive prostate cancer were administered abiraterone acetate and prednisolone with ADT or ADTàalone., Data Collection and Analysis: Two review authors independently classified studies and abstracted data from the included studies. We performed statistical analyses using a random-effects model. We rated the quality of evidence according to the GRADE approach., Main Results: The search identified two randomized controlled trials (RCT), with 2201 men, who were assigned to receive either abiraterone acetate 1000 mg once daily and low dose prednisone (5mg) in addition to ADT, or ADT alone. In the LATITUDE trial, the median age and range of men in the intervention group was 68 (38 to 89) years, and 67 (33 to 92) years in the control group. Nearly all of the men in thisàstudy (97.6%) had prostate cancer with a Gleason score of at least 8 (ISUP grade group 4). Primary outcomes The addition of abiraterone acetate to ADT reduces the probability of death from any cause compared to ADT alone (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.56 to 0.73; 2 RCTs, 2201 men; high certainty of evidence); this corresponds to 163 fewer deaths per 1000 men with hormone-sensitive metastaticàprostate cancerà(210 fewer to 115 fewer) at five years. Abiraterone acetate in addition to ADT probably results in little to no differenceàin quality of life compared to ADT alone, measured with the Functional Assessment of Cancer Therapy-prostate total score (FACT-P; range 0 to 156; higher values indicates better quality of life),àat 12 months (mean difference [MD] 2.90 points, 95% CI 0.11 to 5.60; 1 RCT, 838 men; moderate certainty of evidence). Secondary outcomes Abiraterone plus ADT increases the risk of grades III to V adverse events compared to ADT alone (risk ratio [RR] 1.34, 95% CI 1.22 to 1.47; 1 RCT, 1199 men; high certainty of evidence); this corresponds to 162 more grade III to Vàevents per 1000 men with hormone-sensitive metastaticàprostate cancerà(105 more to 224 more) at a median follow-up of 30àmonths. Abiraterone acetate in addition to ADT probably reduces the probability of death due to prostate cancer compared to ADT alone (HR 0.58, 95% CI 0.50 to 0.68; 2 RCTs, 2201 men; moderate certainty of evidence). This corresponds to 120 fewer death from prostate cancer per 1000 men with hormone-sensitive metastaticàprostate cancerà(95% CI 145 fewer to 90 fewer) afteràa median follow-up of 30 months. The addition of abiraterone acetate to ADT probably decreases the probability of disease progression compared to ADT alone (HR 0.35, 95%CI 0.26 to 0.49; 2 RCTs, 2097 men; moderate certainty of evidence). This corresponds to 369 fewer incidences of disease progression per 1000 men with hormone-sensitive metastaticàprostate cancerà(456 fewer to 256 fewer)àafter a median follow-up of 30 months. The addition of abiraterone acetate to ADT probably increases the risk of discontinuing treatment due to adverse events compared to ADT alone (RR 1.50, 95% CI 1.17 to 1.92; 1 RCT, 1199 men; moderate certainty of evidence). This corresponds to 51 more men (95% CI 17 more to 93 more) discontinuing treatment because of adverse events per 1000 men treated with abiraterone acetate and ADT compared to ADT alone afteràa median follow-up of 30 months., Authors' Conclusions: The addition of abiraterone acetate to androgen deprivation therapy improves overall survival but probably not quality of life. Itàprobably also extends disease-specific survival, and delays disease progression compared to androgen deprivation therapy alone. However, the risk of grades III to V adverse events is increased, and probably, so is the risk of discontinuing treatment due to adverse events., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Purpose: Apalutamide is a next-generation androgen receptor (AR) inhibitor approved for patients with nonmetastatic castration-resistant prostate cancer (CRPC) and metastatic castration-sensitive prostate cancer. We evaluated the pharmacokinetics, safety, and antitumor activity of apalutamide combined with abiraterone acetate plus prednisone (AA-P) in patients with metastatic CRPC (mCRPC)., Patients and Methods: Multicenter, open-label, phase Ib drug-drug interaction study conducted in 57 patients with mCRPC treated with 1,000 mg abiraterone acetate plus 10 mg prednisone daily beginning on cycle 1 day 1 (C1D1) and 240 mg apalutamide daily starting on C1D8 in 28-day cycles. Serial blood samples for pharmacokinetic analysis were collected on C1D7 and C2D8., Results: Systemic exposure to abiraterone, prednisone, and prednisolone decreased 14%, 61%, and 42%, respectively, when apalutamide was coadministered with AA-P. No increase in mineralocorticoid excess-related adverse events was observed. Patients without prior exposure to AR signaling inhibitors had longer median treatment duration and greater mean decrease in prostate-specific antigen (PSA) from baseline compared with those who had received prior therapy. Confirmed PSA reductions of ≥50% from baseline at any time were observed in 80% (12/15) of AR signaling inhibitor-naïve patients and 14% (6/42) of AR signaling inhibitor-treated patients., Conclusions: Treatment with apalutamide plus AA-P was well tolerated and showed evidence of antitumor activity in patients with mCRPC, including those with disease progression on AR signaling inhibitors. No clinically significant pharmacokinetic interaction was observed between abiraterone and apalutamide; however, apalutamide decreased exposure to prednisone. These data support development of 1,000 mg abiraterone acetate plus 10 mg prednisone daily with 240 mg apalutamide daily in patients with mCRPC., (©2020 American Association for Cancer Research.)

Objectives:  Disease progression in metastatic castration-resistant prostate cancer (mCRPC) is dependent on androgen signaling. This case describes the complex adaptive androgen signaling mechanisms in mCRPC and illustrates that caution should be exercised when treating these patients with drugs influencing the androgen axis. Methods:  Single case report and review of the literature. Results:  We report the case of an 86-year-old man with mCRPC, treated with the secondary antihormonal agent abiraterone acetate. Following association of spironolactone to deal with symptoms related to mineralocorticoid excess, biochemical and radiographic disease progression occurred. Spironolactone was discontinued and 8 months after withdrawal, the patient continues to show a biochemical response to abiraterone. Conclusions:  Although spironolactone generally exerts anti-androgenic effects, experimental evidence exists that it acts as an androgen receptor agonist in an androgen-depleted environment, capable of inducing prostate cancer proliferation. This is supported by the observations described in this case report. Therefore, spironolactone should be avoided in prostate cancer patients suffering from treatment-associated side effects of abiraterone.

Background: To describe the patterns of second-line treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel treatment in a Spanish population, to identify the factors associated with those patterns, and to compare the efficacy and safety of the treatments most frequently administered., Methods: Observational, prospective study conducted in patients with histologically or cytologically confirmed prostate adenocarcinoma; documented metastatic castration-resistant disease; progression after first-line, docetaxel-based chemotherapy with or without other agents., Results: Of the 150 patients recruited into the study, 100 patients were prescribed abiraterone acetate plus prednisone (AAP), 44 patients received cabazitaxel plus prednisone (CP), and 6 patients received other treatments. Age (odds ratio [OR] 1.06, 95% [confidence interval] CI 1.01 to 1.11) and not elevated lactate dehydrogenase (LDH) levels (OR 0.33, 95% CI 0.14 to 0.76) were independently associated with the administration of AAP. Treatment with AAP was associated with significantly longer clinical/radiographic progression-free survival (hazard ratio [HR] 0.57, 95% CI 0.38 to 0.85) and overall survival (OS; HR 0.40, 95% CI 0.21 to 0.76) compared to CP, while no significant differences between the treatments were found regarding biochemical progression-free survival (PFS; HR 0.78 [95% CI 0.49 to 1.24]). However, in a post-hoc Cox regression analysis adjusted for potential confounders there were not differences between AAP and CP in any of the time-to-event outcomes, including overall survival. We observed no new safety signals related to either regimen., Conclusion: Second-line AAP for patients with mCRPC is the most common treatment strategy after progression with a docetaxel-based regimen. When controlling for potential confounders, patients receiving this treatment showed no differences in PFS and OS in comparison to those receiving CP, although these latter results should be confirmed in randomized controlled trials.

We report two elderly patients receiving peritoneal dialysis with castration-resistant prostate cancer (CRPC). Herein, we show that the patients were safely treated using abiraterone acetate (750 mg/day orally once daily) and prednisolone (5 mg/day orally once daily). Although the prostate-specific antigen (PSA) level increased in both cases, there was no manifestation of disease progression (clinical and radiographic) for 22 months in case 1 and 8 months in case 2. In case 2, the only adverse event was hypokalemia, which was treated using potassium preparations.

Objectives: To evaluate the efficacy and safety of abiraterone acetate plus prednisone (AAP) plus androgen-deprivation therapy (ADT) in Japanese subgroup with newly diagnosed, metastatic hormone-naïve prostate cancer (mHNPC) from Phase 3, randomized, global LATITUDE study., Methods: Men with mHNPC having ≥2 of 3 high-risk factors (Gleason score ≥8, ≥3 bone lesions or measurable visceral metastases) randomly received abiraterone acetate 1000-mg+ prednisone 5-mg+ADT (AAP group) or ADT+Placebos (Placebo group). Coprimary endpoints were overall survival (OS) and radiographic progression-free survival (rPFS)., Results: Of total 1199 patients in the LATITUDE study, 70 (5.8%) were Japanese (n = 35 each in the AAP and placebo group). After a median follow-up of 35.02 months (range: 2.5-42.3), median OS was not reached in both AAP group and placebo group (HR: 0.635; 95% CI, 0.152-2.659) and the median length of rPFS was not reached in the AAP group and was 22 months in the placebo group (HR:0.219; 95% CI, 0.086-0.560). The most frequently reported adverse events (>20% in either group) in the Japanese subgroup were hypertension, nasopharyngitis, weight increased, hypokalemia, hot flush, back pain, hyperglycemia, ALT and AST elevation. The incidence of Grade 3 or 4 adverse events was 65.7% (23/35) in the AAP group and 20% (7/35) in the placebo group. The efficacy and safety findings of Japanese subgroup were consistent with that of the overall study population., Conclusion: Treatment with AAP plus ADT has shown a positive risk-benefit balance and may serve as a new treatment option to improve the prognosis of Japanese mHNPC patients with high-risk features.

Background/aim: The main purpose of this study was to evaluate the outcome of patients with prostate-specific antigen (PSA) progression after abiraterone acetate (AA) treatment for metastatic castration-resistant prostate cancer (mCRPC)., Patients and Methods: Between 2012 and 2017, 83 patients with clinically-confirmed mCRPC previously treated with docetaxel with/without cabazitaxel followed by AA were included in this retrospective study. All patients received 1,000 mg AA with 5 or 10 mg prednisolone. Among them, 59 were eligible for this study based on PSA progression during the clinical course. Patients were divided into two groups, AA responders and AA non-responders according to previous PSA response to AA treatment. Overall survival and treatment response to subsequent therapy were analyzed., Results: The median overall survival of the 59 patients after AA-treated PSA progression was 12 (95% confidence interval(CI)=7.6-16.4) months and was longer in the AA-responding group compared to the non-responding group (25 vs. 8 months, p<0.001). The survival time after PSA progression on AA was longer in the AA-responsive group despite not being statistically different (13 vs. 7 months, p=0.126). Patients with AA treatment who received subsequent therapies after PSA progression had better overall survival than those without (18 vs. 4 months, p=0.003). In addition, there was a trend for better chemotherapy response in AA non-responders than AA responders, 62.5% (5/8) vs. 12.5% (1/8) respectively., Conclusion: In our small retrospective patient experience, effective sequential treatments for patients with mCRPC provided overall survival benefit. Previous treatment response can act as a clinical predictor for subsequent treatment., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Primary resistance to abiraterone acetate (AA), a key medication for the treatment of metastatic castration-resistant prostate cancer, occurs in 20% to 40% of patients. We aim to identify predictive biomarkers for AA-treatment response and understand the mechanisms related to treatment resistance. Experimental Design: We used the Infinium Human Methylation 450K BeadChip to monitor modification profiles of cell-free circulating DNA (cfDNA) in 108 plasma samples collected from 33 AA-treated patients. Results: Thirty cytosines showed significant modification differences (FDR Q < 0.05) between AA-sensitive and AA-resistant patients during the treatment, of which 21 cytosines were differentially modified prior to treatment. In addition, AA-sensitive patients, but not AA-resistant patients, lost interindividual variation of cfDNA modification shortly after starting AA treatment, but such variation returned to initial levels in the later phases of treatment. Conclusions: Our findings provide a list of potential biomarkers for predicting AA-treatment response, highlight the prognostic value of using cytosine modification variance as biomarkers, and shed new insights into the mechanisms of prostate cancer relapse in AA-sensitive patients. Clin Cancer Res; 24(14); 3317-24. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Among all cancer-related death, prostate cancer accounts for the second prominent reason for cancer-associated death in men. Despite the castration mediated reduction in testosterone synthesis, adrenal glands, as well as tissues of prostate cancer, continue to produce androgens, which ultimately lead to the growth of prostate cancer. This phase is referred as metastatic castration-resistant prostate cancer, which throws an obstacle to treatment. Androgen antagonists, in addition to deprivation of hormone, is being used for reducing the level of prostate-specific antigen but has not successfully come in front as a choice for prolonging the life of patients suffering from prostate cancer. In this prevailing scenario, abiraterone acetate (AA) has proved to be a boon for patients suffering from prostate cancer. AA selectively inhibits the actions of enzymes C17, 20-lyase and 17α-hydroxylase on cytochrome P450 (CYP) 17 when administered orally. The signaling of androgen receptor, being important for primary to metastatic phases of prostate cancer, CYP17 is essential for the synthesis of androgen. Herein, the in-detail pharmacological profile of AA, including androgen signaling, mechanism of action of AA, mechanism of AA resistance, pharmacokinetics, latest clinical findings, predictive markers, optimal treatment sequence, toxicity, and food interaction profiles have been reviewed., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC + AAP versus SOC + DocP., Method: Recruitment to SOC + DocP and SOC + AAP overlapped November 2011 to March 2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for ≥2 years and RT to the primary tumour. Stratified randomisation allocated pts 2 : 1 : 2 to SOC; SOC + docetaxel 75 mg/m2 3-weekly×6 + prednisolone 10 mg daily; or SOC + abiraterone acetate 1000 mg + prednisolone 5 mg daily. AAP duration depended on stage and intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison. A hazard ratio (HR) <1 favours SOC + AAP, and HR > 1 favours SOC + DocP., Results: A total of 566 consenting patients were contemporaneously randomised: 189 SOC + DocP and 377 SOC + AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8-10; 449 (79%) WHO performance status 0; median age 66 years and median PSA 56 ng/ml. With median follow-up 4 years, 149 deaths were reported. For overall survival, HR = 1.16 (95% CI 0.82-1.65); failure-free survival HR = 0.51 (95% CI 0.39-0.67); progression-free survival HR = 0.65 (95% CI 0.48-0.88); metastasis-free survival HR = 0.77 (95% CI 0.57-1.03); prostate cancer-specific survival HR = 1.02 (0.70-1.49); and symptomatic skeletal events HR = 0.83 (95% CI 0.55-1.25). In the safety population, the proportion reporting ≥1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC + DocP, and 40%, 7% and 1% SOC + AAP; prevalence 11% at 1 and 2 years on both arms. Relapse treatment patterns varied by arm., Conclusions: This direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events. Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs., Trial Registration: Clinicaltrials.gov: NCT00268476.

Objectives: Treatment landscape in prostate cancer has changed dramatically with the emergence of new medicines in the past few years. The traditional survival partition model (SPM) cannot accurately predict long-term clinical outcomes because it is limited by its ability to capture the key consequences associated with this changing treatment paradigm. The objective of this study was to introduce and validate a discrete-event simulation (DES) model for prostate cancer., Methods: A DES model was developed to simulate overall survival (OS) and other clinical outcomes based on patient characteristics, treatment received, and disease progression history. We tested and validated this model with clinical trial data from the abiraterone acetate phase III trial (COU-AA-302). The model was constructed with interim data (55% death) and validated with the final data (96% death). Predicted OS values were also compared with those from the SPM., Results: The DES model's predicted time to chemotherapy and OS are highly consistent with the final observed data. The model accurately predicts the OS hazard ratio from the final data cut (predicted: 0.74; 95% confidence interval [CI] 0.64-0.85 and final actual: 0.74; 95% CI 0.6-0.88). The log-rank test to compare the observed and predicted OS curves indicated no statistically significant difference between observed and predicted curves. However, the predictions from the SPM based on interim data deviated significantly from the final data., Conclusions: Our study showed that a DES model with properly developed risk equations presents considerable improvements to the more traditional SPM in flexibility and predictive accuracy of long-term outcomes., (Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Aim: The aim of this study is to evaluate cardiotoxicity of abiraterone acetate (AA) in metastatic castration-resistant prostate cancer patients (pts) with cardiovascular comorbidities or coronary artery disease (CAD) risk factors., Patients & Methods: We prospectively analyzed pts receiving AA in order to evaluate correlations between cardiotoxicity onset and CAD risk factors or cardiovascular comorbidities., Results: Eighty-seven pts were enrolled, with median treatment duration of 9 months (1-44). At baseline, 84 pts (96%) had CAD risk factors. During treatment four pts (4; 6%) developed hypertension and 26 pts (30%) worsened the preexisting hypertension. Median left ventricular ejection fraction were 64 and 63% at baseline and after treatment, respectively., Conclusion: AA appears to be safe in pts with cardiovascular comorbidities or CAD risk factors.

Background: To evaluate the safety and efficacy of abiraterone acetate (AA) in the "real life" clinical practice for men with chemotherapy-naïve metastatic castration-resistant prostate., Methods: A consecutive series of patients with mCRPC in 9 Italian tertiary centres treated with AA was collected. Demographics, clinical parameters, treatment outcomes and toxicity were recorded. The Brief Pain Inventory scale Q3 was tracked and patient treatment satisfaction was evaluated. Survival curves were estimated by the method of Kaplan-Meier and Cox regression and compared by the log-rank test statistic., Results: We included 145 patients (mean age 76.5y). All patients were on androgen deprivation therapy. Patients had prior radiotherapy, radical prostatectomy, both treatments or exclusive androgen deprivation therapy in 17%, 33%, 9% and 40%, respectively. 57% of the patients had a Gleason score higher more than 7 at diagnosis. 62% were asymptomatic patients. The median serum total PSA at AA start was 17 ng/mL (range 0,4-2100). The median exposure to AA was 10 months (range 1-35). The proportion of patients achieving a PSA decline ≥50% at 12 weeks was 49%. Distribution of patient satisfaction was 32% "greatly improved", 38% "improved", 24% "not changed", 5.5% "worsened". Grade 3 and 4 toxicity was recorded in 17/145 patients 11.7% (70% cardiovascular events, 30% critical elevation of AST/ALT levels). At the last follow-up, median progression free and overall survival were 17 and 26.5 months, respectively. Both outcomes significantly correlated with the presence of pain, patient satisfaction, PSA baseline and PSA decline., Conclusions: The AA is effective and well tolerated in asymptomatic or slightly symptomatic mCRPC in a "real life" setting. The survival outcomes are influenced by the presence of pain, patient satisfaction, baseline PSA and PSA decline., Trial Registration: The study was retrospectively registered at ISRCTN as DOI: 10.1186/ISRCTN 52513758 in date April the 30th 2016.

Background: The value of continuation of luteinizing hormone-releasing hormone (LHRH) therapy in castration-resistant prostate cancer (CRPC) remains controversial and clear evidence is lacking. Argumentation for cessation of LHRH therapy is the prolonged suppression of testosterone levels after the withdrawal of LHRH analogues and the fact that disease progression occurs despite castration levels of testosterone. Especially upon treatment with the life-prolonging cytochrome P450 17-alpha-hydroxylase (Cyp17)-inhibitor, abiraterone, which has the ability to further suppress testosterone serum levels over LHRH therapy alone, continuation of LHRH therapy seems to be negligible. However, the proven increase of luteinizing hormone levels after LHRH withdrawal, which is even further increased by abiraterone, may counteract the effects of abiraterone by the induction of enzymes of steroidogenesis. Therefore, cessation of LHRH therapy when starting treatment with abiraterone in CRPC may display an unpredictable hazard to the patients. This study will explore the role of continuation of LHRH therapy when starting treatment with abiraterone in patients with asymptomatic or mildly symptomatic, chemotherapy-naïve CPRC., Methods/design: The trial will assess radiographic progression-free survival after 12 months of treatment with abiraterone/prednisone in patients who will be randomized to receive continuing LHRH therapy versus LHRH withdrawal at the time of starting abiraterone therapy., Discussion: This multicenter, prospective, randomized, exploratory phase-II trial will bring about new data regarding the efficacy and safety of abiraterone/prednisone treatment with or without continuation of LHRH therapy. In addition, further insight into the complex hormonal changes under treatment will be gained and the results of this trial may give rise to a larger phase-III trial to examine the possibility of withdrawing LHRH therapy in patients with CRPC., Trial Registration: ClinicalTrials.gov, ID: NCT02077634 . Registered on 9 December 2013.

Purpose: To evaluate the efficacy of apalutamide before or after treatment with abiraterone acetate and prednisone (AAP) in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). Experimental Design: Two cohorts were studied: AAP-naïve and post-AAP patients who had received ≥6 months of AAP. Patients had progressive mCRPC per rising prostate-specific antigen (PSA) and/or imaging, without prior chemotherapy exposure. All received apalutamide 240 mg/day. Primary endpoint was ≥50% decline in 12-week PSA according to Prostate Cancer Working Group 2 criteria. Secondary endpoints included time to PSA progression and time on treatment. Results: Forty-six patients enrolled in the AAP-naïve ( n = 25) and post-AAP ( n = 21) cohorts. The 12-week PSA response rate was 88% (22/25) and 22% (4/18), median time to PSA progression was 18.2 months [95% confidence interval (CI), 8.3 months-not reached) and 3.7 months (95% CI, 2.8-5.6 months), and median time on treatment 21 months (range, 2.6-37.5) and 4.9 months (range, 1.3-23.2), for the AAP-naïve and post-AAP cohorts, respectively. Eighty percent (95% CI, 59-93) and 64% (95% CI, 43-82) of AAP-naïve and 43% (95% CI, 22-66) and 10% (95% CI, 1-30) of post-AAP patients remained on treatment for 6+ and 12+ months, respectively. Common treatment-emergent adverse events in both cohorts were grade 1 or 2 fatigue, diarrhea, nausea, and abdominal pain. Conclusions: Apalutamide was safe, well tolerated, and demonstrated clinical activity in mCRPC, with 80% of AAP-naïve and 43% of post-AAP patients, remaining on treatment for 6 months or longer. Clin Cancer Res; 23(14); 3544-51. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Lessons Learned: The combination of standard dose abiraterone acetate and BEZ235, a pan-class I PI3K and mTORC1/2 inhibitor, was poorly tolerated in men with progressive mCRPC.Although the clinical development of BEZ235 has been discontinued in prostate cancer, agents that more selectively target PI3K-AKT-mTOR signaling may have a more favorable therapeutic index and should continue to be explored., Background: Androgen receptor (AR) and phosphatidylinositol-3 kinase (PI3K) signaling are two commonly perturbed pathways in prostate cancer. Preclinical data have shown that the two pathways compensate for each other when one is inhibited, and combined inhibition of AR and PI3K signaling may be a viable strategy to prevent or overcome castration resistance., Methods: This phase I study evaluated the safety and tolerability of abiraterone acetate and prednisone combined with BEZ235, a dual PI3K and mTORC1/2 inhibitor, in men with progressive metastatic castration resistant prostate cancer (mCRPC) who have not received prior chemotherapy., Results: Six patients ( n  = 6) were treated at the starting dose level of abiraterone acetate 1,000 mg with prednisone 5 mg twice daily and BEZ235 200 mg twice daily in a 3 + 3 dose escalation design. The study was terminated early because three of the six patients (50%) experienced dose-limiting toxicities: grade 3 mucositis, grade 3 hypotension, and grade 4 dyspnea and pneumonitis. All six patients had previously progressed on abiraterone/prednisone. The median treatment duration was 27 days (range: 3-130 days). No prostate-specific antigen (PSA) decline or objective response were observed., Conclusion: The combination of standard-dose abiraterone/prednisone with BEZ235 200 mg twice daily was poorly tolerated in patients with mCRPC. The on-target and off-target effects of dual PI3K and mTORC inhibition likely contributed to the unacceptable toxicity profile. The Oncologist 2017;22:503-e43., (© AlphaMed Press; the data published online to support this summary is the property of the authors.)

Lessons Learned: The safety and activity findings of abiraterone acetate plus prednisone treatment in black men with mCRPC were similar to results from previously conducted studies with largely white populations.Poor trial accrual continues to be a challenge in black men with mCRPC and further efforts are needed to address such underrepresentation., Background: Self-identified black men have higher incidence and mortality from prostate cancer in the United States compared with white men but are dramatically underrepresented in clinical trials exploring novel therapies for metastatic castration-resistant prostate cancer (mCRPC)., Methods: Black men with mCRPC were treated with abiraterone acetate (AA), 1,000 mg daily, and prednisone (P), 5 mg twice daily. The primary objective was to determine antitumor activity (defined by a ≥30% decline in prostate-specific antigen [PSA] level) and to correlate germline polymorphisms in androgen metabolism genes with antitumor activity. Secondary objectives included determining safety, post-treatment changes in measurable disease, and time to disease progression., Results: From April 2013 to March 2016, a total of 11 black men were enrolled and received AA plus P (AA+P); 7 of 10 evaluable patients were docetaxel naive. Post-treatment declines in PSA level of ≥30% were achieved in 90% of patients. The side effect profile was consistent with prior clinical trials exploring AA+P in mCRPC. Due to poor accrual, the study was closed prematurely with insufficient sample size for the planned pharmacogenetic analyses., Conclusion: In this small prospective study terminated for poor accrual, the safety and activity of AA+P in black men with mCRPC was similar to that reported in prior studies exploring AA in largely white populations. Further efforts are needed to address underrepresentation of black men in mCRPC trials., (©AlphaMed Press; the data published online to support this summary is the property of the authors.)

Background: Few prognostic models for overall survival (OS) are available for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with recently approved agents. We developed a prognostic index model using readily available clinical and laboratory factors from a phase III trial of abiraterone acetate (hereafter abiraterone) in combination with prednisone in post-docetaxel mCRPC., Patients and Methods: Baseline data were available from 762 patients treated with abiraterone-prednisone. Factors were assessed for association with OS through a univariate Cox model and used in a multivariate Cox model with a stepwise procedure to identify those of significance. Data were validated using an independent, external, population-based cohort., Results: Six risk factors individually associated with poor prognosis were included in the final model: lactate dehydrogenase > upper limit of normal (ULN) [hazard ratio (HR) = 2.31], Eastern Cooperative Oncology Group performance status of 2 (HR = 2.19), presence of liver metastases (HR = 2.00), albumin ≤4 g/dl (HR = 1.54), alkaline phosphatase > ULN (HR = 1.38) and time from start of initial androgen-deprivation therapy to start of treatment ≤36 months (HR = 1.30). Patients were categorized into good (n = 369, 46%), intermediate (n = 321, 40%) and poor (n = 107, 13%) prognosis groups based on the number of risk factors and relative HRs. The C-index was 0.70 ± 0.014. The model was validated by the external dataset (n = 286)., Conclusion: This analysis identified six factors used to model survival in mCRPC and categorized patients into three distinct risk groups. Prognostic stratification with this model could assist clinical practice decisions for follow-up and monitoring, and may aid in clinical trial design., Trial Registration Numbers: NCT00638690., (© Janssen R&D 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

Background: COU-AA-301 trial has proved that abiraterone acetate (AA), a selective inhibitor of androgen biosynthesis, improved overall survival (OS) of patients with metastatic castration resistant prostate cancer (mCRPC) after a first line of docetaxel. Based on this result, a Temporary Authorization for Use (TAU) was performed between December 2010 and July 2011 to provide patients with mCRPC the opportunity to receive AA before its commercialization. The aim of this study was to evaluate safety and efficacy of AA treatment in this TAU., Methods: Between December 2010 and July 2011, we conducted an ambispective, multicentric cohort study and investigated data from 20 centres participating to the AA TAU for patients presenting mCRPC and already treated by a first line of chemotherapy (CT). Statistical analyses of the data were performed using the Stata software v13 to identify predictive and prognostic factors., Results: Among the 408 patients, 306 were eligible with a follow-up at 3 years. Median OS was 37.1 months from beginning of CT and 14.6 months from AA introduction. 211 patients (69%) received ≥ 3 months of AA and 95 patients (31%) were treated less than 3 months. In the multivariate analyses, duration of AA was significantly correlated with PSA decrease at 3 months. Additionally, shorter time under AA treatment, presence of multiple sites of metastasis and previous hormonal treatment duration were three independent factors associated with poorer OS. At the time of analysis ten patients were still under treatment for more than 3 years., Conclusions: Biochemical response monitored by PSA changes at 3 months is a strong predictive factor for AA treatment duration. Some high responders' patients could beneficiate from AA for more than 3 years.