Evaluation of circulating tumor cell (CTC) enumeration as an efficacy response biomarker of overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC): Planned final analysis (FA) of COU-AA-301, a randomized double-blind, placebo-controlled phase III study of abiraterone acetate (AA) plus low-dose prednisone (P) post docetaxel.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. LBA4517-LBA4517 ◽  
Author(s):  
H. I. Scher ◽  
G. Heller ◽  
A. Molina ◽  
T. S. Kheoh ◽  
G. Attard ◽  
...  
Keyword(s):  
Final Analysis ◽  
Circulating Tumor Cell ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Castration Resistant ◽  
Response Biomarker ◽  
Phase Iii Study ◽  
Dose Prednisone

Exploratory analysis of survival benefit and prior docetaxel (D) treatment in COU-AA-301, a phase III study of abiraterone acetate (AA) plus prednisone (P) in metastatic castration-resistant prostate cancer (mCRPC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4558-4558 ◽  
Author(s):  
Oscar B. Goodman ◽  
Kim N. Chi ◽  
Arturo Molina ◽  
Christopher Logothetis ◽  
Robert J. Jones ◽  
...  
Keyword(s):  
Abiraterone Acetate ◽  
Phase Iii ◽  
Double Blind Study ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Survival Result ◽  
Castration Resistant ◽  
Phase Iii Study ◽  
Previously Treated ◽  
Post Hoc

4558 Background: AA, a selective androgen biosynthesis inhibitor, blocks the action of CYP17, thereby inhibiting adrenal and intratumoral androgen production. AA has demonstrated improved overall survival (OS) by 4.6 months (mos) vs placebo (HR=0.74) in patients (pts) previously treated with D. Methods: COU-AA-301 is a randomized double blind study of AA (1 g) + P (5 mg po BID) vs placebo + P administered to mCRPC pts post-D with a primary endpoint of OS. To further evaluate primary survival result robustness, we performed post hoc exploratory analyses to assess whether the timing of first and last dose of D and reason for D discontinuation impacted OS. Results: At randomization, treatment arms were balanced with respect to baseline characteristics, prior D use, and reasons for discontinuation. In both arms, almost half (45%) discontinued D due to progressive disease (PD); remainder discontinued D after completing all planned cycles (37%), due to toxicity (12%), or for other reasons (5%) per investigator. Median OS from first and last dose of D were longer with AA vs placebo (Table). Median OS was longer with AA vs placebo in pts who discontinued D for PD, or for all other reasons. Conclusions: These exploratory analyses suggest that the OS benefit of AA in mCRPC was maintained when calculated from first or last dose of prior D, and whether or not pts discontinued D for PD. Pts in AA arm of this study had a prolonged median OS of > 32 mos from time of initial D therapy. Congruity among these analyses and lack of dependence on D timing demonstrate robustness of the primary survival result. [Table: see text]

scholarly journals Randomized, Double-Blind, Placebo-Controlled Phase III Study of Tasquinimod in Men With Metastatic Castration-Resistant Prostate Cancer

2016 ◽  
Vol 34 (22) ◽  
pp. 2636-2643 ◽  
Author(s):  
Cora Sternberg ◽  
Andrew Armstrong ◽  
Roberto Pili ◽  
Siobhan Ng ◽  
Robert Huddart ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
End Point ◽  
Castration Resistant ◽  
Phase Iii Study

Purpose Tasquinimod, a novel oral therapy targeting the tumor microenvironment, significantly improved progression-free survival (PFS) in a randomized, placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). This phase III study was conducted to confirm the phase II results and to detect an overall survival (OS) benefit. Patients and Methods Men with chemotherapy-naïve mCRPC and evidence of bone metastases were assigned (2:1) to receive tasquinimod once per day or placebo until progression or toxicity. The primary end point was radiographic PFS (rPFS; time from random assignment to radiologic progression or death) per Prostate Cancer Working Group 2 criteria and RECIST 1.1. The study had 99.9% power to detect an rPFS hazard ratio (HR) of 0.6 with a two-sided alpha error of .05 and 80% power to detect a target HR of 0.8 for OS, the key secondary end point. Results In all, 1,245 patients were randomly assigned to either tasquinimod (n = 832) or placebo (n = 413) between March 2011 and December 2012 at 241 sites in 37 countries. Baseline characteristics were balanced between groups: median age, 71 years; Karnofsky performance status ≥ 90%, 77.3%; and visceral metastases, 21.1%. Estimated median rPFS by central review was 7.0 months (95% CI, 5.8 to 8.2 months) with tasquinimod and 4.4 months (95% CI, 3.5 to 5.5 months) with placebo (HR, 0.64; 95% CI, 0.54 to 0.75; P < .001). Median OS was 21.3 months (95% CI, 19.5 to 23.0 months) with tasquinimod and 24.0 months (95% CI, 21.4 to 26.9 months) with placebo (HR, 1.10; 95% CI, 0.94 to 1.28; P = .25). Grade ≥ 3 adverse events were more frequent with tasquinimod (42.8% v 33.6%), the most common being anemia, fatigue, and cancer pain. Conclusion In chemotherapy-naïve men with mCRPC, tasquinimod significantly improved rPFS compared with placebo. However, no OS benefit was observed.

Improved survival outcomes in clinically relevant patient subgroups from COU-AA-301, a phase III study of abiraterone acetate (AA) plus prednisone (P) in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel-based chemotherapy.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 4-4 ◽  
Author(s):  
H. I. Scher ◽  
C. Logothetis ◽  
A. Molina ◽  
O. B. Goodman ◽  
C. N. Sternberg ◽  
...  
Keyword(s):  
Abiraterone Acetate ◽  
Phase Iii ◽  
Double Blind Study ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Androgen Synthesis ◽  
Phase Iii Study ◽  
Study Population ◽  
Grade 3 ◽  
Patient Subgroups

4 Background: AA is a selective androgen biosynthesis inhibitor that blocks the action of CYP17. Preclinical and early clinical studies suggest that AA potently inhibits persistent androgen synthesis from adrenal and intratumoral sources, thus suppressing an important growth stimulus for mCRPC. Methods: COU-AA-301 ( NCT00638690 ) is an international, randomized, double blind study of AA (1,000 mg + P 5 mg po BID) vs placebo + P administered to men with mCRPC progressing after docetaxel-based chemo. OS is the primary endpoint. Patients treated with previous ketoconazole or > 2 prior chemo regimens were excluded. Results: Data are drawn from a planned, stratified interim analysis, unblinded in August 2010, based on significant OS improvement in the AA + P treatment group compared to the placebo + P group [median OS 14.8 vs.10.9 months; HR = 0.646 (0.54-0.77), P < 0.0001]. A subgroup analysis for OS is presented in the table. Mineralocorticoid- related AEs were more common in the AA arm vs placebo: fluid retention 30.5% vs 22.3%, hypokalemia 17.1% vs 8.4%; but grade 3/4 hypokalemia (3.8% vs 0.8%), and grade 3/4 hypertension (1.3% vs 0.3%) were infrequent. LFT abnormalities were observed in 10.4% AA vs 8.1% placebo; and cardiac disorders were observed in 13.3% AA vs 10.4% placebo. Conclusions: AA significantly prolongs OS in patients with mCRPC who have progressed after docetaxel-based chemo. AA's favorable treatment effect on OS, observed across multiple patient subgroups (HR range 0.59 – 0.74 vs placebo + P), was consistent with the survival benefit for the overall study population. [Table: see text] [Table: see text]

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 KEYNOTE-921: Phase III study of pembrolizumab plus docetaxel for metastatic castration-resistant prostate cancer

2021 ◽  
Author(s):  
Daniel P Petrylak ◽  
Raffaele Ratta ◽  
Rustem Gafanov ◽  
Gaetano Facchini ◽  
Josep M Piulats ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Options ◽  
Unmet Need ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Castration Resistant ◽  
Previously Treated

Despite recent advances, treatment options for men with metastatic castration-resistant prostate cancer (mCRPC) progressing after next-generation hormonal agents (NHAs) are limited and provide only modest survival benefit. Thus, an unmet need remains for mCRPC patients after treatment with targeted endocrine therapy or NHA therapy. Pembrolizumab, a humanized monoclonal antibody for PD-1, has been found to have activity as monotherapy in patients with mCRPC and as combination therapy in a Phase Ib/II study with docetaxel and prednisone/prednisolone for patients previously treated with enzalutamide or abiraterone acetate. The aim of the randomized, double-blind, Phase III KEYNOTE-921 study is to evaluate the efficacy and safety of pembrolizumab plus docetaxel in patients with mCRPC who were previously treated with an NHA. Clinical trial registration: NCT03834506 ( ClinicalTrials.gov )

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