scholarly journals A prognostic model for stratifying clinical outcomes in chemotherapy-naive metastatic castration-resistant prostate cancer patients treated with abiraterone acetate

2017 ◽  
Vol 12 (2) ◽  
pp. E47-52 ◽  
Author(s):  
Daniel Joseph Khalaf ◽  
Claudia M. Avilés ◽  
Arun A. Azad ◽  
Katherine Sunderland ◽  
Tilman Todenhöfer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Group Performance ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Prognostic Index ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Progression

Introduction: Recently, a prognostic index including six risk factors (RFs) (unfavourable Eastern Cooperative Oncology Group performance status [ECOG PS], presence of liver metastases, short response to luteinizing hormone-releasing hormone [LHRH] agonists/ antagonists, low albumin, increased alkaline phosphatase [ALP] and lactate dehydrogenase [LDH]) was developed from the COUAA- 301 trial in post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate. Our primary objective was to evaluate this model in a cohort of chemotherapy-naive mCRPC patients receiving abiraterone.Methods: We identified 197 chemotherapy-naive patients who received abiraterone at six BC Cancer Agency centres and who had complete information on all six RFs. Study endpoints were prostate-specific antigen (PSA) response rate (RR), time to PSA progression, time on treatment, and overall survival (OS). PSA RR and survival outcomes were compared using Χ2 test and log-rank test. Multivariable Cox proportional hazard analysis was performed to identify RFs independently associated with OS.Results: Patients were classified into good (0‒1 RFs), intermediate (2‒3 RFs), and poor (4‒6 RFs) prognostic groups (33%, 52%, and 15%, respectively). For good-, intermediate-, and poor-risk patients, PSA RR (≥50% decline) was 60% vs. 42% vs. 40% (p=0.05); median time to PSA progression was 7.3 vs. 5.3 vs. 5.0 months (p=0.02); and median OS was 29.4 vs. 13.8 vs. 8.7 months (p<0.0001).Conclusions: The six-factor prognostic index model stratifies clinical outcomes in chemotherapy-naive mCRPC patients treated with abiraterone. Identifying patients at risk of poor outcome is important for informing clinical practice and clinical trial design.

Clinical activity of abiraterone acetate in patients with castration-resistant prostate cancer who received prior ketoconazole therapy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 99-99 ◽  
Author(s):  
Bo Zhao ◽  
Jorge A. Garcia ◽  
Timothy D. Gilligan ◽  
Brian I. Rini ◽  
Robert Dreicer
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Underlying Mechanism ◽  
Abiraterone Acetate ◽  
Clinical Activity ◽  
Drug Discontinuation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Response ◽  
Psa Progression

99 Background: Studies have shown activity of Abiraterone acetate (AA) in patients (pts) with castration-resistant prostate cancer (CRPC) who have received prior ketoconazole. Prostate-specific antigen (PSA) response to AA in relation to previous PSA response to ketoconazole was investigated. Methods: A retrospective analysis was conducted to determine the clinical activity of AA in men with CRPC who have received prior ketoconazole therapy at our institution. Time to PSA progression (PSA TTP) was defined by PCWG2 criteria, a PSA reduction of 50% or more was considered as PSA response. Results: Thirty four pts were identified. Nineteen pts (56%) had previous PSA responses on ketoconazole, with a median PSA TTP of 11 months (95% confidence interval [CI] 6.8-19.9). Subsequently, 11 of 34 (33%) of pts achieved a PSA response on AA, with a median PSA TTP of 6 months (95% CI 4.9-9.5). Among the 19 pts having a PSA response on ketoconazole, only four (21%) pts subsequently had PSA response to AA. Two of these pts had transient PSA response with PSA TTP less than 3 months on kKetoconazole, one patient discontinued Ketoconazole due to side effects, one patient had intermittent non-castrate testosterone levels. In contrast, 7 of 15 (46.7%) pts without prior PSA response to ketoconazole subsequently achieved PSA response on AA (p=0.11). Of note, PSA reduction of less than 50% on AA was observed in 9 of 34 pts (26%), which was associated with a longer median PSA TTP compared to pts who had PSA-progressive disease (5.9 months [95% CI 3.5-7.3] vs.1.5 months [95% CI 1.0-3.5], p=0.028). Five of these nine patients had a prior PSA response to ketoconazole but required drug discontinuation for reasons other than disease progression. Conclusions: PSA response to prior ketoconazole therapy is associated with lower PSA response rate to subsequent AA. The observation suggests that there is a biologically distinct subset of patients who are ketoconazole-resistant but abiraterone-sensitive, the underlying mechanism needs to be further investigated.

scholarly journals A multicentre analysis of abiraterone acetate in Canadian patients with metastatic castration resistant prostate cancer

2014 ◽  
Vol 8 (9-10) ◽  
pp. 583 ◽  
Author(s):  
Ravinder Clayton ◽  
Jackson Wu ◽  
Daniel Y Heng ◽  
Scott A North ◽  
Urban Emmenegger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Castration Resistant ◽  
Study Results

Introducton: The COU-AA-301 trial showed that abiraterone acetate (abiraterone), an oral cytochrome p450 CYP17 inhibitor, improved survival for men with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel. To better understand the non-clinical trial experience with abiraterone, we undertook a multicentre retrospective analysis of Canadian mCRPC patients treated with abiraterone.Methods: Consecutive patients with mCRPC who received abiraterone post-docetaxel were identified using centralized pharmacy records. These patients came from 5 Canadian tertiary cancer centres. Patients who received abiraterone for approved indications were included. Demographics, prognostic factors, treatment outcomes and adverse events were abstracted.Results: We included 187 patients who initiated abiraterone between January 2011 and June 2012. The median age at diagnosis and abiraterone start was 65 and 73 years, respectively. Seventy-three (39%) patients had metastatic disease at diagnosis. The Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 and 3 was noted in 17, 96, 39 and 8 patients, respectively. The median prostate-specific antigen (PSA) at abiraterone start was 132, with a median PSA doubling time of 2.8 months. The median follow-up of patients still on active follow-up was 13 months. The proportion of patients achieving a ≥50% PSA reduction was 64/177 (36%). PSA progression-free survival was 3.5 months (95% confidence interval [CI], 3.0, 4.0). Median overall survival from start of abiraterone was 11 months (95% CI, 8.0, 13) and 38 months (95% CI, 31, 41) from date of mCRPC. Anemia and fatigue were the most commonly reported adverse events.Conclusions: This study carries the inherent limitations of a retrospective chart review. The outcomes in this series of men treated with abiraterone in a non-trial setting were expected, considering previous clinical trials. Our results, therefore, support the generalizability of the COU-AA-301 study results.

Randomized Phase II Study of Docetaxel and Prednisone With or Without OGX-011 in Patients With Metastatic Castration-Resistant Prostate Cancer

2010 ◽  
Vol 28 (27) ◽  
pp. 4247-4254 ◽  
Author(s):  
Kim N. Chi ◽  
Sebastien J. Hotte ◽  
Evan Y. Yu ◽  
Dongsheng Tu ◽  
Bernhard J. Eigl ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Experimental Therapy ◽  
Clinical Activity ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Purpose To determine the clinical activity of OGX-011, an antisense inhibitor of clusterin, in combination with docetaxel/prednisone in patients with metastatic castration-resistant prostate cancer. Patients and Methods Patients were randomly assigned 1:1 to receive docetaxel/prednisone either with (arm A) or without (arm B) OGX-011 640 mg intravenously weekly. The primary end point was the proportion of patients with a prostate-specific antigen (PSA) decline of ≥ 50% from baseline, with the experimental therapy being considered of interest if the proportion of patients with a PSA decline was more than 60%. Secondary end points were objective response rate, progression-free survival (PFS), overall survival (OS), and changes in serum clusterin. Results Eighty-two patients were accrued, 41 to each arm. OGX-011 adverse effects included rigors and fevers. After cycle 1, median serum clusterin decreased by 26% in arm A and increased by 0.9% in arm B (P < .001). PSA declined by ≥ 50% in 58% of patients in arm A and 54% in arm B. Partial response occurred in 19% and 25% of patients in arms A and B, respectively. Median PFS and OS times were 7.3 months (95% CI, 5.3 to 8.8 months) and 23.8 months (95% CI, 16.2 months to not reached), respectively, in arm A and 6.1 months (95% CI, 3.7 to 8.6 months) and 16.9 months (95% CI, 12.8 to 25.8 months), respectively, in arm B. Baseline factors associated with improved OS on exploratory multivariate analysis were an Eastern Cooperative Oncology Group performance status of 0 (hazard ratio [HR], 0.27; 95% CI, 0.14 to 0.51), presence of bone or lymph node metastases only (HR, 0.45; 95% CI, 0.25 to 0.79), and treatment assignment to OGX-011 (HR, 0.50; 95% CI, 0.29 to 0.87). Conclusion Treatment with OGX-011 and docetaxel was well tolerated with evidence of biologic effect and was associated with improved survival. Further evaluation is warranted.

scholarly journals Serum Androgens As Prognostic Biomarkers in Castration-Resistant Prostate Cancer: Results From an Analysis of a Randomized Phase III Trial

2013 ◽  
Vol 31 (22) ◽  
pp. 2791-2798 ◽  
Author(s):  
Charles J. Ryan ◽  
Arturo Molina ◽  
Jinhui Li ◽  
Thian Kheoh ◽  
Eric J. Small ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Group Performance ◽  
Short Form ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Phase Iii ◽  
Double Blind Study ◽  
Castration Resistant Prostate Cancer ◽  
Baseline Serum ◽  
Castration Resistant

Purpose In the phase III study COU-AA-301, abiraterone acetate (AA) plus prednisone (P) prolonged overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel administration. In this article, we investigate the relationship between baseline serum androgen (SA) levels and OS. Patients and Methods COU-AA-301 is a randomized, double-blind study of AA (1,000 mg every day) plus P (5 mg by mouth twice daily; n = 797) versus P alone (n = 398). Randomization was stratified by Eastern Cooperative Oncology Group performance status (0 to 1 v 2), pain (Brief Pain Inventory-Short Form over past 24 hours: 4 to 10, present; v 0 to 3, absent), prior chemotherapy (1 v 2), and progression (prostate-specific antigen v radiographic). Association of baseline SA (testosterone, androstenedione, dehydroepiandrosterone sulfate), was measured by ultrasensitive liquid-liquid extraction or protein precipitation and two-dimensional liquid chromatography coupled to mass spectrometry, with OS determined by bivariate and multivariable Cox models. OS was examined with SA as greater than median and less than or equal to the median. Results Median survival increased with each quartile increase in testosterone level regardless of treatment arm. SA levels at baseline strongly associated with survival (P < .0001) in bivariate and multivariable analyses. Longer survival was observed for patients with SA above median compared with below median in both the AA and P arms (eg, testosterone, AA; hazard ratio, 0.64; 95% CI, 0.53 to 0.77; P < .0001). Treatment with AA led to longer survival versus P alone in the above- or below-median group for all androgens. Conclusion SA, measured with a novel ultrasensitive assay in COU-AA-301, is prognostic for OS and may be useful for risk stratification in mCRPC clinical trials.

scholarly journals Significant and Sustained Antitumor Activity in Post-Docetaxel, Castration-Resistant Prostate Cancer With the CYP17 Inhibitor Abiraterone Acetate

2010 ◽  
Vol 28 (9) ◽  
pp. 1489-1495 ◽  
Author(s):  
Alison H.M. Reid ◽  
Gerhardt Attard ◽  
Daniel C. Danila ◽  
Nikhil Babu Oommen ◽  
David Olmos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Phase Ii ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
End Point ◽  
Castration Resistant ◽  
Psa Progression

Purpose The principal objective of this trial was to evaluate the antitumor activity of abiraterone acetate, an oral, specific, irreversible inhibitor of CYP17 in docetaxel-treated patients with castration-resistant prostate cancer (CRPC). Patients and Methods In this multicenter, two-stage, phase II study, abiraterone acetate 1,000 mg was administered once daily continuously. The primary end point was achievement of a prostate-specific antigen (PSA) decline of ≥ 50% in at least seven of 35 patients. Per an attained phase II design, more than 35 patients could be enrolled if the primary end point was met. Secondary objectives included: PSA declines of ≥ 30% and ≥ 90%; rate of RECIST (Response Evaluation Criteria in Solid Tumors) responses and duration on study; time to PSA progression; safety and tolerability; and circulating tumor cell (CTC) enumeration. Results Docetaxel-treated patients with CRPC (N = 47) were enrolled. PSA declines of ≥ 30%, ≥ 50% and ≥ 90% were seen in 68% (32 of 47), 51% (24 of 47), and 15% (seven of 47) of patients, respectively. Partial responses (by RECIST) were reported in eight (27%) of 30 patients with measurable disease. Median time to PSA progression was 169 days (95% CI, 113 to 281 days). The median number of weeks on study was 24, and 12 (25.5%) of 47 patients remained on study ≥ 48 weeks. CTCs were enumerated in 34 patients; 27 (79%) of 34 patients had at least five CTCs at baseline. Eleven (41%) of 27 patients had a decline from at least five to less than 5 CTCs, and 18 (67%) of 27 had a ≥ 30% decline in CTCs after starting treatment with abiraterone acetate. Abiraterone acetate was well tolerated. Conclusion Abiraterone acetate has significant antitumor activity in post-docetaxel patients with CRPC. Randomized, phase III trials of abiraterone acetate are underway to define the future role of this agent.

scholarly journals Abiraterone Alone or in Combination With Enzalutamide in Metastatic Castration-Resistant Prostate Cancer With Rising Prostate-Specific Antigen During Enzalutamide Treatment

2018 ◽  
Vol 36 (25) ◽  
pp. 2639-2646 ◽  
Author(s):  
Gerhardt Attard ◽  
Michael Borre ◽  
Howard Gurney ◽  
Yohann Loriot ◽  
Corina Andresen-Daniil ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Control Group ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Psa Progression

Purpose Enzalutamide resistance could result from raised androgens and be overcome by combination with abiraterone acetate. PLATO ( ClinicalTrials.gov identifier: NCT01995513) interrogated this hypothesis using a randomized, double-blind, placebo-controlled design. Patients and Methods In period one, men with chemotherapy-naïve metastatic castration-resistant prostate cancer received open-label enzalutamide 160 mg daily. Men with no prostate-specific antigen (PSA) increase at weeks 13 and 21 were treated until PSA progression (≥ 25% increase and ≥ 2 ng/mL above nadir), then randomly assigned at a one-to-one ratio in period two to abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily with either enzalutamide or placebo (combination or control group, respectively) until disease progression as defined by the primary end point: progression-free survival (radiographic or unequivocal clinical progression or death during study). Secondary end points included time to PSA progression and PSA response in period two. Results Of 509 patients enrolled in period one, 251 were randomly assigned in period two. Median progression-free survival was 5.7 months in the combination group and 5.6 months in the control group (hazard ratio, 0.83; 95% CI, 0.61 to 1.12; P = .22). There was no difference in the secondary end points. Grade 3 hypertension (10% v 2%) and increased ALT (6% v 2%) or AST (2% v 0%) were more frequent in the combination than the control group. Conclusion Combining enzalutamide with abiraterone acetate and prednisone is not indicated after PSA progression during treatment with enzalutamide alone; hypertension and elevated liver enzymes are more frequent with combination therapy.

Cabazitaxel Versus Docetaxel As First-Line Therapy for Patients With Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase III Trial—FIRSTANA

2017 ◽  
Vol 35 (28) ◽  
pp. 3189-3197 ◽  
Author(s):  
Stéphane Oudard ◽  
Karim Fizazi ◽  
Lisa Sengeløv ◽  
Gedske Daugaard ◽  
Fred Saad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Purpose In patients with metastatic castration-resistant prostate cancer (mCRPC), overall survival (OS) is significantly improved with cabazitaxel versus mitoxantrone after prior docetaxel treatment. FIRSTANA ( ClinicalTrials.gov identifier: NCT01308567) assessed whether cabazitaxel 20 mg/m2 (C20) or 25 mg/m2 (C25) is superior to docetaxel 75 mg/m2 (D75) in terms of OS in patients with chemotherapy-naïve mCRPC. Patients and Methods Patients with mCRPC and Eastern Cooperative Oncology Group performance status of 0 to 2 were randomly assigned 1:1:1 to receive C20, C25, or D75 intravenously every 3 weeks plus daily prednisone. The primary end point was OS. Secondary end points included safety; progression-free survival (PFS); tumor, prostate-specific antigen, and pain response; pharmacokinetics; and health-related quality of life. Results Between May 2011 and April 2013, 1,168 patients were randomly assigned. Baseline characteristics were similar across cohorts. Median OS was 24.5 months with C20, 25.2 months with C25, and 24.3 months with D75. Hazard ratio for C20 versus D75 was 1.01 (95% CI, 0.85 to 1.20; P = .997), and hazard ratio for C25 versus D75 was 0.97 (95% CI, 0.82 to 1.16; P = .757). Median PFS was 4.4 months with C20, 5.1 months with C25, and 5.3 months with D75, with no significant differences between treatment arms. Radiographic tumor responses were numerically higher for C25 (41.6%) versus D75 (30.9%; nominal P = .037, without multiplicity test adjustment). Rates of grade 3 or 4 treatment-emergent adverse events were 41.2%, 60.1%, and 46.0% for C20, C25, and D75, respectively. Febrile neutropenia, diarrhea, and hematuria were more frequent with C25; peripheral neuropathy, peripheral edema, alopecia, and nail disorders were more frequent with D75. Conclusion C20 and C25 did not demonstrate superiority for OS versus D75 in patients with chemotherapy-naïve mCRPC. Tumor response was numerically higher with C25 versus D75; pain PFS was numerically improved with D75 versus C25. Cabazitaxel and docetaxel demonstrated different toxicity profiles, with overall less toxicity with C20.

scholarly journals Randomized, Double-Blind, Placebo-Controlled Phase III Trial Comparing Docetaxel and Prednisone With or Without Bevacizumab in Men With Metastatic Castration-Resistant Prostate Cancer: CALGB 90401

2012 ◽  
Vol 30 (13) ◽  
pp. 1534-1540 ◽  
Author(s):  
William Kevin Kelly ◽  
Susan Halabi ◽  
Michael Carducci ◽  
Daniel George ◽  
John F. Mahoney ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Phase Iii ◽  
Controlled Study ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Purpose A randomized, placebo-controlled study based on preclinical and clinical data that supports the potential role of vascular endothelial growth factor in prostate cancer was performed to evaluate the addition of bevacizumab to standard docetaxel and prednisone therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods Patients with chemotherapy-naive progressive mCRPC with Eastern Cooperative Oncology Group performance status ≤ 2 and adequate bone marrow, hepatic, and renal function were randomly assigned to receive docetaxel 75 mg/m2 intravenously (IV) over 1 hour for 21 days plus prednisone 5 mg orally twice per day (DP) with either bevacizumab 15 mg/kg IV every 3 weeks (DP + B) or placebo. The primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), 50% decline in prostate-specific antigen, objective response (OR), and toxicity. Results In total, 1,050 patients were randomly assigned. The median OS for patients given DP + B was 22.6 months compared with 21.5 months for patients treated with DP (hazard ratio, 0.91; 95% CI, 0.78 to 1.05; stratified log-rank P = .181). The median PFS time was superior in the DP + B arm (9.9 v 7.5 months, stratified log-rank P < .001) as was the proportion of patients with OR (49.4% v 35.5%; P = .0013). Grade 3 or greater treatment-related toxicity was more common with DP + B (75.4% v 56.2%; P ≤ .001), as was the number of treatment-related deaths (4.0% v 1.2%; P = .005). Conclusion Despite an improvement in PFS and OR, the addition of bevacizumab to docetaxel and prednisone did not improve OS in men with mCRPC and was associated with greater toxicity.

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