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.

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.

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 Phase II Multicenter Study of Abiraterone Acetate Plus Prednisone Therapy in Patients With Docetaxel-Treated Castration-Resistant Prostate Cancer

2010 ◽  
Vol 28 (9) ◽  
pp. 1496-1501 ◽  
Author(s):  
Daniel C. Danila ◽  
Michael J. Morris ◽  
Johann S. de Bono ◽  
Charles J. Ryan ◽  
Samuel R. Denmeade ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Circulating Tumor Cell ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Castration Resistant

Purpose Persistence of ligand-mediated androgen receptor signaling has been documented in castration-resistant prostate cancers (CRPCs). Abiraterone acetate (AA) is a potent and selective inhibitor of CYP17, which is required for androgen biosynthesis in the testes, adrenal glands, and prostate tissue. This trial evaluated the efficacy and safety of AA in combination with prednisone to reduce the symptoms of secondary hyperaldosteronism that can occur with AA monotherapy. Patients and Methods Fifty-eight men with progressive metastatic CRPC who experienced treatment failure with docetaxel-based chemotherapy received AA (1,000 mg daily) with prednisone (5 mg twice daily). Twenty-seven (47%) patients had received prior ketoconazole. The primary outcome was ≥ 50% prostate-specific antigen (PSA) decline, with objective response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and changes in Eastern Cooperative Oncology Group (ECOG) performance status (PS) and circulating tumor cell (CTC) numbers. Safety was also evaluated. Results A ≥ 50% decline in PSA was confirmed in 22 (36%) patients, including 14 (45%) of 31 ketoconazole-naïve and seven (26%) of 27 ketoconazole-pretreated patients. Partial responses were seen in four (18%) of 22 patients with RECIST-evaluable target lesions. Improved ECOG PS was seen in 28% of patients. Median time to PSA progression was 169 days (95% CI, 82 to 200 days). CTC conversions with treatment from ≥ 5 to < 5 were noted in 10 (34%) of 29 patients. The majority of AA-related adverse events were grade 1 to 2, and no AA-related grade 4 events were seen. Conclusion AA plus prednisone was well tolerated, with encouraging antitumor activity in heavily pretreated CRPC patients. The incidence of mineralocorticoid-related toxicities (hypertension or hypokalemia) was reduced by adding low-dose prednisone. The combination of AA plus prednisone is recommended for phase III investigations.

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 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.

scholarly journals Overall Survival of Black and White Men With Metastatic Castration-Resistant Prostate Cancer Treated With Docetaxel

2019 ◽  
Vol 37 (5) ◽  
pp. 403-410 ◽  
Author(s):  
Susan Halabi ◽  
Sandipan Dutta ◽  
Catherine M. Tangen ◽  
Mark Rosenthal ◽  
Daniel P. Petrylak ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Black Men ◽  
Performance Status ◽  
Specific Antigen ◽  
White Men ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Black And White ◽  
Castration Resistant

Purpose Several studies have reported that among patients with localized prostate cancer, black men have a shorter overall survival (OS) time than white men, but few data exist for men with advanced prostate cancer. The primary goal of this analysis was to compare the OS in black and white men with metastatic castration-resistant prostate cancer (mCRPC) who were treated in phase III clinical trials with docetaxel plus prednisone (DP) or a DP-containing regimen. Methods Individual participant data from 8,820 men with mCRPC randomly assigned in nine phase III trials to DP or a DP-containing regimen were combined. Race was based on self-report. The primary end point was OS. The Cox proportional hazards regression model was used to assess the prognostic importance of race (black v white) adjusted for established risk factors common across the trials (age, prostate-specific antigen, performance status, alkaline phosphatase, hemoglobin, and sites of metastases). Results Of 8,820 men, 7,528 (85%) were white, 500 (6%) were black, 424 (5%) were Asian, and 368 (4%) were of unknown race. Black men were younger and had worse performance status, higher testosterone and prostate-specific antigen, and lower hemoglobin than white men. Despite these differences, the median OS was 21.0 months (95% CI, 19.4 to 22.5 months) versus 21.2 months (95% CI, 20.8 to 21.7 months) in black and white men, respectively. The pooled multivariable hazard ratio of 0.81 (95% CI, 0.72 to 0.91) demonstrates that overall, black men have a statistically significant decreased risk of death compared with white men ( P < .001). Conclusion When adjusted for known prognostic factors, we observed a statistically significant increased OS in black versus white men with mCRPC who were enrolled in these clinical trials. The mechanism for these differences is not known.

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.

Is the duration of castration resistance predictive for sequential treatment responses in the metastatic castration-resistant prostate cancer setting?

2020 ◽  
pp. 107815522095161
Author(s):  
Özgecan Dülgar ◽  
Deniz Tataroğlu Özyükseler ◽  
Mustafa Başak ◽  
Seval Ay ◽  
Deniz Tural ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Real World Data ◽  
Ecog Performance Status ◽  
Castration Resistant ◽  
One Year

Objective Prostate cancer is the second leading cause of cancer death in men. Androgen deprivation therapy (ADT) has been the primary therapeutic approach for treatment of prostate cancer. However,nearly all patients develop the castration-resistant disease . We evaluated real-world data with abiraterone and enzalutamide treatment. By this data, we aimed to analyze whether that prior short response to ADT could predict response to subsequent therapy with androgen receptor axis targeted agent (ARATA). Material and Method We collected data from two cancer centers, 151 consecutive patients with treated abiraterone or enzalutamide in the first line of metastatic castration resistant prostat cancer (mCRPC) setting were included. The patients who received docetaxel in castration naive setting is also included. Time to castration resistance (TTCR) was defined as the duration from the initial to failure of primary ADT. Results Patients with treated ARATA were divided into two groups according to the time to castration resistance (TTCR). Patients who became resistant to ADT up to one year had a median PFS of 6.6 months, compared to median PFS of 13.3 months for patients who responded ADT for more than 1 year. (p = 0.002). In the post-docetaxel setting, median PFS is 12.6 months of patients with treated ARATA who had TTCR for more than one year, and median PFS is 6.6 months in those who had TTCR less than one year (p = 0.007).Univariate and multivariate analyses were performed to determine the clinical factors on ARATA outcomes. Eastern Cooperative Oncology Group (ECOG) performance status(PS), median prostate-specific antigen(PSA) and time to CRPC were significantly predicted outcomes of ARATA on multivariate analysis. Conclusion TTCR is also a predictor for PFS of the patients who were treated ARATA both whole cohort and post-docetaxel.

Previous enzalutamide therapy and response to subsequent taxane therapy in metastatic castration-resistant prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 227-227 ◽  
Author(s):  
Marco Gizzi ◽  
Giulia Baciarello ◽  
Aude Flechon ◽  
Philippe Beuzeboc ◽  
Antoine Angelergues ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Objective Response ◽  
Specific Antigen ◽  
Phase Iii ◽  
Cross Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Response ◽  
Pretreated Patients ◽  
The Impact

227 Background: Cross-resistance between taxanes and androgen receptor axis targeted agents is a matter of debate in metastatic castration-resistant prostate cancer (mCRPC). Preclinical data about response to taxanes after prior enzalutamide suggest some level of cross-resistance (van Soest et al, Eur J Cancer 2013) though this was not confirmed in other models (Al Nakouzi N, Eur Urol 2014). The first objective of this study was to assess the impact of previous enzalutamide therapy on the efficacy of subsequent taxane-based chemotherapy. The second objective was to investigate the prognosis of patients when chemotherapy was initiated in enzalutamide-pretreated patients. Methods: Data from 96 enzalutamide- and placebo-treated patients enrolled in the Prevail phase III trial were retrospectively collected from 14 centers in France. Changes in prostate specific antigen (PSA) levels, progression free survival (PFS) and RECIST criteria v 1.1 were used to determine the activity of docetaxel (n=89) or cabazitaxel (n=7) treatment. The Halabi model was used to predict survival probabilities for the enzalutamide- or placebo-pretreated patients when chemotherapy was initiated (Halabi et al, J Clin Oncol 2014). Results: Overall, 96 patients were included in this analysis (58 in the placebo arm vs. 38 in enzalutamide arm). PSA response to taxanes (defined as a decline of ≥50% from baseline) was marginally lower in enzalutamide-vs. placebo-pretreated patients (34% vs. 53%, p=0.10). PSA response in enzalutamide-pretreated patients was not different from that observed with docetaxel given every 3 weeks in TAX 327 trial (Tannock et al, NEJM 2004) (45%, p=0.20, binomial test). Median PFS and objective response rates were similar between the two groups (4.8m vs 6.7 m;p=0.14 and 45% vs 43%;p=0.83 respectively). Halabi score was well-balanced between the two groups (p=0.30). Conclusions: Taxanes retain efficacy in enzalutamide-pretreated mCRPC. At the time of first-line taxane-based chemotherapy initiation, the prognosis of enzalutamide-treated patients according to the Halabi score was not different from that of enzalutamide-naïve patients.

Abiraterone acetate plus prednisone (AAP) in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) and prior diethylstilbestrol (DES) therapy: Preliminary results.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 235-235
Author(s):  
Diogo Assed Bastos ◽  
Marcos Tobias Machado ◽  
Renato Panhoca ◽  
Giovani Thomaz Pioner ◽  
Gustavo Werutsky ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Group Performance ◽  
Performance Status ◽  
Prospective Trial ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Psa Response

235 Background: AAP is approved for patients with chemotherapy-naïve mCRPC, but the population with previous use of DES was not studied before. DES is a commonly used hormone therapy for mCRPC in second and plus lines, especially in developing countries, due to lack of access to novel and efficacious therapies. The objective of this trial is to describe the efficacy and safety of AAP after DES treatment in patients who are chemotherapy-naïve, potentially affecting chemotherapy onset. This is the first and only prospective trial to show this data. Methods: This phase 2 multicenter, open-label single-arm study evaluated 46 patients receiving AA (1000 mg daily) + low-dose prednisone (P; 10 mg daily) and androgen deprivation therapy in patients with DES–refractory mCRPC enrolled from Oct 2014 to Oct 2015. The primary efficacy endpoint was time to prostate-specific antigen progression (PSAP) by Prostate Cancer Working Group (PCWG2) criteria. Secondary endpoints included PSA response (≥50% reduction), overall survival, and safety. Results: At baseline, median age was 69 years, median PSA was 40 ng/mL, there were no visceral metastases, 98% of patients had Eastern Cooperative Oncology Group Performance Status 0-1, and 44% had Gleason scores ≥7. Thirty two subjects (71.1%) had PSAP. PSA response was achieved by 47% of patients at week 12 and 56% at any time. Three patients remain on study drug and 4 are in follow-up. AA treatment continued until PSAP, clinical progression, consent withdrawal, or unacceptable toxicity. The median duration of study treatment was 8.6 months. The median time to PSAP was 7.4 months (95% CI = 5.6-9.4) and the median overall survival was 25.6 months (95% CI = 15.7-NE). Treatment-related adverse events included hypertension (19.6%), hyperglycemia (19.6%), fatigue (17.4%), and hypokalemia (4.5%); most grade 1-2. Conclusions: The present study confirmed that AAP provides PSA responses even in heavily treated patients, showing clinical benefit post-DES in chemotherapy-naive mCRPC patients. It also confirmed tolerability of AAP, with an easily manageable toxicity profile. Clinical trial information: NCT02217566.

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