scholarly journals One-Year, Open-Label Extension Study on the Safety and Efficacy of Abiraterone Acetate Fine Particle Formulation in Patients With Metastatic Castration-Resistant Prostate Cancer

2020 ◽  
Vol 13 ◽  
pp. 117956112091012
Author(s):  
Jillian Chapas-Reed ◽  
Cy Stein ◽  
Nicholas Squittieri ◽  
Raoul Concepcion
Keyword(s):  
Fine Particle ◽  
Specific Antigen ◽  
Serum Testosterone ◽  
Abiraterone Acetate ◽  
Extension Study ◽  
Phase 2 ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Castration Resistant ◽  
Open Label Extension

Purpose: Abiraterone acetate is an androgen synthesis inhibitor used to treat metastatic castration-resistant prostate cancer. The therapeutic equivalence, pharmacokinetics, and safety of abiraterone acetate fine particle (AAFP) versus originator abiraterone acetate (OAA) were examined in a Phase-2 study; sufficient similarity was observed between the 2 treatments. This 1-year, open-label, extension study evaluated the long-term safety and efficacy of AAFP. Patients and methods: This was an open-label, single-arm extension study. Patients who completed the 84-day, Phase-2, run-in study could enroll to receive 500 mg AAFP once daily and 4 mg methylprednisolone twice daily for up to 1 year. Safety was the primary endpoint, as assessed by adverse event monitoring throughout the study. Secondary efficacy endpoints included change from run-in study baseline levels of serum testosterone and prostate-specific antigen measured at baseline, 6 months, and 1 year. Results: Twenty patients enrolled, of whom 9 and 11 received prior AAFP and OAA in the run-in study, respectively. Both prior treatment groups maintained a significant decrease in serum testosterone from run-in baseline at all timepoints; mean change from run-in baseline ± standard deviation at 1 year of −6.24 ± 2.02 ( P = .0023) and −5.87 ± 3.64 ( P = .0026) ng/dL for the prior AAFP and OAA group, respectively. Change from run-in baseline in serum prostate-specific antigen was not significant. Most (84.0%) adverse events were Grade 1 or 2. Conclusion: No new safety signals were identified, and patients were able to successfully switch from OAA to AAFP with no impact.

Phase I Clinical Trial of a Selective Inhibitor of CYP17, Abiraterone Acetate, Confirms That Castration-Resistant Prostate Cancer Commonly Remains Hormone Driven

2008 ◽  
Vol 26 (28) ◽  
pp. 4563-4571 ◽  
Author(s):  
Gerhardt Attard ◽  
Alison H.M. Reid ◽  
Timothy A. Yap ◽  
Florence Raynaud ◽  
Mitch Dowsett ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Phase I ◽  
Specific Antigen ◽  
Serum Testosterone ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Mineralocorticoid Receptor Antagonist ◽  
Androgen Synthesis ◽  
Castration Resistant

Purpose Studies indicate that castration-resistant prostate cancer (CRPC) remains driven by ligand-dependent androgen receptor (AR) signaling. To evaluate this, a trial of abiraterone acetate—a potent, selective, small-molecule inhibitor of cytochrome P (CYP) 17, a key enzyme in androgen synthesis—was pursued. Patients and Methods Chemotherapy-naïve men (n = 21) who had prostate cancer that was resistant to multiple hormonal therapies were treated in this phase I study of once-daily, continuous abiraterone acetate, which escalated through five doses (250 to 2,000 mg) in three-patient cohorts. Results Abiraterone acetate was well tolerated. The anticipated toxicities attributable to a syndrome of secondary mineralocorticoid excess—namely hypertension, hypokalemia, and lower-limb edema—were successfully managed with a mineralocorticoid receptor antagonist. Antitumor activity was observed at all doses; however, because of a plateau in pharmacodynamic effect, 1,000 mg was selected for cohort expansion (n = 9). Abiraterone acetate administration was associated with increased levels of adrenocorticotropic hormone and steroids upstream of CYP17 and with suppression of serum testosterone, downstream androgenic steroids, and estradiol in all patients. Declines in prostate-specific antigen ≥ 30%, 50%, and 90% were observed in 14 (66%), 12 (57%), and 6 (29%) patients, respectively, and lasted between 69 to ≥ 578 days. Radiologic regression, normalization of lactate dehydrogenase, and improved symptoms with a reduction in analgesic use were documented. Conclusion CYP17 blockade by abiraterone acetate is safe and has significant antitumor activity in CRPC. These data confirm that CRPC commonly remains dependent on ligand-activated AR signaling.

A randomized trial of abiraterone acetate (AA) administered with 1 of 4 glucocorticoid (GC) regimens in metastatic castration-resistant prostate cancer (mCRPC) patients (pts).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 261-261 ◽  
Author(s):  
Gerhardt Attard ◽  
Axel S. Merseburger ◽  
Cora N. Sternberg ◽  
Linda Cerbone ◽  
Federica Recine ◽  
...  
Keyword(s):  
Response Rate ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Phase 2 Trial ◽  
Castration Resistant ◽  
Psa Response ◽  
Clinical Trial Information ◽  
Additional Safety

261 Background: AA is approved for mCRPC, coadministered with prednisone (P) (5 mg BID) to prevent adverse events (AEs) associated with mineralocorticoid excess (ME). Lower GC doses had not previously been formally evaluated in combination with AA. Methods: This was an open-label, multicenter, phase 2 trial (NCT01867710) of asymptomatic chemotherapy-naïve mCRPC pts randomized 1:1:1:1 to AA (1000 mg QD) plus P 5 mg BID or P 5 mg QD or P 2.5 mg BID or dexamethasone (DEX) 0.5 mg QD. Pts who had previously received GC or ketoconazole were excluded. The primary end point was no ME (% of pts experiencing neither hypokalemia nor hypertension during the first 24 weeks of treatment).Secondary end points included additional safety, as well as response rate in the first 24 weeks, defined as a decline in prostate-specific antigen (PSA) ≥ 50% confirmed after 4 weeks. Results: 164 pts were randomized; 133 (81.6%) completed 24 weeks’ treatment. Median age: 70 years. Table 1 shows the rates of ME, hypertension, hypokalemia and PSA response. Changes in HbA1c values were minimal and observed in 16 (10.7%) pts. Conclusions: These data suggest that P 5 mg BID, which is approved in combination with AA, and DEX 0.5 mg QD, are effective in preventing ME-associated AEs, and that P 2.5 mg BID and P 5 mg QD can be safely used with appropriate monitoring. The suggestion of a higher PSA response rate with DEX 0.5 mg QD arm warrants further validation. Clinical trial information: NCT01867710. [Table: see text]

Pharmacokinetic (PK) subgroup results from the phase 2 pharmacodynamic and bioequivalence study of abiraterone acetate fine particle formulation (AAFP) in patients with metastatic castration-resistant prostate cancer (mCRPC): The STAAR study.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 176-176
Author(s):  
Curtis Dunshee ◽  
Cy Aaron Stein ◽  
Paul R. Nemeth ◽  
Bill Bosch ◽  
Jillian Chapas-Reed ◽  
...  
Keyword(s):  
Steady State ◽  
Study Drug ◽  
Bioequivalence Study ◽  
Abiraterone Acetate ◽  
Controlled Study ◽  
Phase 2 ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Castration Resistant ◽  
Study Results

176 Background: AAFP, a novel formulation, showed therapeutic equivalence to originator abiraterone acetate (OAA) in the Phase 2 STAAR study (Stein et al. Urologic Oncol). A patient-subgroup analysis compared steady-state PK parameters between AAFP and OAA. Methods: This multicenter, open-label, active-controlled study enrolled men with progressive mCRPC treated 1:1 with 500 mg AAFP tablets QD + 4 mg methylprednisolone BID, or 1000 mg OAA tablets QD + 5 mg prednisone BID for 9 days. Study drug was taken 2 hours post morning meal. On day 9, plasma abiraterone blood samples were collected at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 24 hr time points. Results: PK samples were evaluable for 13 of 14 patients (n=5, AAFP; n=8, OAA). Mean age was 67.4 and 73.3 years, respectively. Twelve patients completed the 12-week study without clinical disease progression. One OAA patient died from MI in week 4. PK parameters (AUC, Cmax, Cmin), were numerically lower but not statistically significantly different for those treated with AAFP vs OAA (Table). Conclusions: Clinical benefit in this subgroup of patients was consistent with the overall study results. High PK variability was observed in both groups. PK parameters were not statistically different between AAFP and OAA. 24-hour PK Parameters at Steady State Clinical trial information: NCT02737332. [Table: see text]

scholarly journals Prognostic factors for patients treated with abiraterone

2020 ◽  
Vol 6 (2) ◽  
pp. FSO436 ◽  
Author(s):  
Cecília M Alvim ◽  
André Mansinho ◽  
Rita S Paiva ◽  
Raquel Brás ◽  
Patrícia M Semedo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Hazard Ratio ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Prognostic And Predictive Factors

Aim: To evaluate prostate-specific antigen response (PSAr) defined as a ≥50% decrease in PSA concentration from the pretreatment value, as a prognostic factor in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). Methods: Retrospective evaluation of patients with mCRPC treated with AA. Results: 124 patients were identified. Median overall survival and progression-free survival for patients achieving PSAr versus patients without PSAr were 29.3 versus 9.7 months and 17.0 versus 5.2 months, respectively. Multivariate analysis confirmed that PSAr correlated with better overall survival (hazard ratio: 0.19; 95% CI: 0.10−0.38; p < 0.001) and progression-free survival (hazard ratio: 0.24; 95% CI: 0.14−0.41; p < 0.001). Conclusion: PSAr can be utilized as prognostic and predictive factors in mCRPC patients treated with AA.

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.

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