Medication patterns of abiraterone acetate plus prednisone or enzalutamide and PSA progression in veterans with metastatic castration-resistant prostate cancer

2021 ◽  
Vol 37 (4) ◽  
pp. 635-642
Author(s):  
Stephen J. Freedland ◽  
Sophia Li ◽  
Dominic Pilon ◽  
Rachel H. Bhak ◽  
Sahil Narkhede ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Progression

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.

Efficacy of abiraterone acetate in the treatment of castration-resistant prostate cancer: Early results from the German compassionate-use program.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15195-e15195
Author(s):  
Carsten Henning Ohlmann ◽  
Michael Stöckle ◽  
David A. Pfister ◽  
Axel Heidenreich ◽  
Axel S. Merseburger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Disease Progression ◽  
Objective Response ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Compassionate Use ◽  
Castration Resistant ◽  
Psa Progression

e15195 Background: Abiraterone acetate (AA) plus prednisone (P) has demonstrated an improved survival of patients with castration-resistant prostate cancer (CRPC) compared to placebo plus P in a large phase III trial. In Germany, patients were able to receive AA within a compassionate-use program (CUP). Here, we report the first results of the program. Methods: Patients were eligible for the CUP if they progressed on or after at least one cytotoxic chemotherapy regimens. For CUP entry, patients were considered to have disease progression if they had radiographic evidence of disease progression in soft tissue or bone with or without PSA-progression and ongoing androgen deprivation. Patients received AA 1000mg daily plus prednisone 5mg BID until progression of disease or unacceptable toxicity. Results: Between 02-05/2011, 398 patients were registered for the CUP in Germany. Data from 191/350 (47.9%) of the patients treated at 10 different sites were available for evaluation of efficacy. Median age was 70.72yrs (52.35-87.61) and patients received a median of 1 (1-4) chemotherapy lines prior to CUP entry. Median PSA at baseline was 220.5 ng/ml (0.47-4245); 168 (88%) of patients presented with bone metastasis. With regard to efficacy, 64/191 (33.5%) of the patients showed an unconfirmed PSA-response ≥50%. At a median follow-up of 5.3 months, 51/191 (26.7%) patients had died, resulting in a median PSA-progression free and overall survival of 8.3 and 10.61 months, respectively. In a subset of patients (71/191, 37.2%) data regarding objective response was available with 25/71 (35.2%) achieving an objective response. Data from 114 pts. revealed fatigue (20.3%), hot flushes (15.8%), edema (10.6%), elevated liver enzymes (8.0%) and asthenia (7.9%) being the most frequent toxicities (any grade). Conclusions: Treatment of CRPC patients with AA outside controlled clinical trials leads to considerable PSA- and objective response rates with a favourable toxicity profile, comparable to the results from COU-AA-301 registration trial. Due to the short median follow-up, conclusions regarding PSA-progression free and overall survival may not be drawn.

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.

CYCLONE 2: A phase II, randomized, placebo-controlled study of abiraterone acetate plus prednisone with or without abemaciclib in patients with metastatic castration-resistant prostate cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS5591-TPS5591
Author(s):  
Matthew Raymond Smith ◽  
Neeraj Agarwal ◽  
Tilman Todenhöfer ◽  
Redas Trepiakas ◽  
Jae-Lyun Lee ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Phase Ii ◽  
Objective Response ◽  
Metastatic Breast ◽  
Abiraterone Acetate ◽  
Controlled Study ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Progression

TPS5591 Background: Despite recent advances, nearly all patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) experience disease progression and cancer-specific mortality. Persistent or reactivated androgen receptor (AR) signaling and/or activation of pathways in cross-talk with AR signaling are key drivers of mCRPC progression. Evidence suggests that AR signaling promotes translation of D-type cyclins resulting in cyclin-dependent kinase 4 and 6 (CDK4&6) activation and cell cycle progression. Abemaciclib is an oral selective inhibitor of CDK4&6 dosed on a continuous schedule, that is FDA-approved in combination with endocrine therapy or as monotherapy to treat HR+, HER2- metastatic breast cancer pts. Preclinical studies with prostate cancer cell lines and xenograft models showed that abemaciclib induces cell cycle arrest and tumor growth inhibition. The hypothesis is that addition of abemaciclib to AR targeted therapy may be an effective treatment for mCRPC pts. Methods: CYCLONE 2 (NCT03706365) is a phase II, randomized, double-blind, multicenter, placebo-controlled study to assess the safety and efficacy of abemaciclib in combination with abiraterone acetate plus prednisone (AA+P) as first-line treatment of pts with mCRPC. The study is designed in two parts. Part 1 is a 30-patient safety lead-in to determine the recommended phase II dose (RP2D; 150 mg or 200 mg, twice daily) of abemaciclib in combination with AA (1000 mg, once daily) + P (5 mg, twice daily). In part 2, 150 pts are randomized 1:1 to abemaciclib at the RP2D with AA+P or placebo with AA+P. Pts who received prior AA+P, enzalutamide, apalutamide, darolutamide, radiopharmaceuticals, or sipuleucel-T are excluded. Prior docetaxel for metastatic hormone-sensitive prostate cancer, but not for mCRPC, is allowed. Pts must have progressive mCRPC (by PSA and/or imaging) and an accessible metastatic lesion for tumor biopsy. The co-primary objectives are radiographic PFS (per RECIST1.1 for soft tissue and PCWG3 for bone) and time to PSA progression. Secondary objectives include safety, objective response rate, duration of response, OS, time to symptomatic progression, and pharmacokinetics. Assuming hazard ratios of 0.64 (rPFS) and 0.6 (PSA progression), the study is powered to 80% and 85%, respectively, to test the superiority of abemaciclib plus AA+P vs. placebo plus AA+P at one-sided α=0.1 using stratified log-rank tests. Part 1 is completed and part 2 is enrolling in 70 sites worldwide. Clinical trial information: NCT03706365 .

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 Outcome of Patients with Metastatic Castration-resistant Prostate Cancer After PSA Progression with Abiraterone Acetate

2018 ◽  
Vol 38 (9) ◽  
pp. 5429-5436
Author(s):  
SHENG-CHUN HUNG ◽  
SHIAN-SHIANG WANG ◽  
JIAN-RI LI ◽  
MEI-CHIH CHEN ◽  
CHENG-KUANG YANG ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Progression

Abiraterone acetate in patients with metastatic castration-resistant prostate cancer, chemo-naive, who received a prior diethylstilbestrol therapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 130-130
Author(s):  
Diogo Assed Bastos ◽  
Giovani Thomaz Pioner ◽  
Renato Panhoca ◽  
Marjo Deninson Cardenuto Perez ◽  
Ronaldo Damião ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Median Time ◽  
Abiraterone Acetate ◽  
Serum Testosterone Level ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Response ◽  
Psa Progression ◽  
Serum Androgens

130 Background: The use of diethylstilbestrol (DES) for the treatment of metastatic castration resistant prostate cancer (mCRPC) is very common in developing countries. Retrospective data suggests that abiraterone acetate (AA) is active in patients that progressed to DES. This phase II study evaluated the efficacy and safety of abiraterone acetate in chemotherapy-naïve patients with metastatic CRPC who have progressed to DES. Methods: Patients with DES−refractory metastatic CRPC with ongoing ADT, serum testosterone level < 50 ng/dL and ECOG of 0-2 were included. All patients received AA 1,000 mg with prednisone 5 mg once daily in a 28 days cycles. The primary endpoint was the time to PSA progression (PSAP) by PCWG2 and was previously reported. We present here secondary endpoints: overall survival, PSA response, maximum PSA change from baseline and safety. Results: A total of 46 patients were enrolled, median age was 69.8 years, 76% had gleason > = 7 at diagnosis, median time from metastatic disease to DES discontinuation was 25.9 months, and a median duration of prior DES of 7.2 months. AA treatment resulted in median time to PSA progression of 7.3 months. PSA response rate (³ 50%) was 47.5% (95% CI: 36,1% to 68,5%) at 12 weeks and 57.5% (95% CI: 27.0% to 59.1%) at any time. 93.4% received chemotherapy after progression to AA. The median overall survival was 29.6 months. Substantial declines in serum androgens from baseline to week 12 occurred and in this group a higher proportion of PSA responses occurred. The incidence of adverse events (AEs) related to AA was 74% and prednisone 59%. Hypertension (21.7%), fatigue (19.6%) and oedema peripheral (13.0%) were the most frequent AA related AEs. The most frequent prednisone related AEs were hyperglycaemia (15.2%) hypertension (10.9%). Serious AEs occurred in 23.9% of subjects and 3 subjects (6.5%) died of AEs not related to study drugs. Conclusions: AA is well tolerated and demonstrated activity in mCRPC patients previously treated with DES, therefore it should be considered an option in chemo-naïve patients. Serum androgens levels tend to decrease with AA treatment and are associated with PSA responses. Clinical trial information: NCT02217566.

Sign in / Sign up

Export Citation Format

Share Document