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Randomized Controlled Trial
. 2013 Jan 10;368(2):138-48.
doi: 10.1056/NEJMoa1209096. Epub 2012 Dec 10.

Abiraterone in metastatic prostate cancer without previous chemotherapy

Charles J Ryan  1 , Matthew R Smith, Johann S de Bono, Arturo Molina, Christopher J Logothetis, Paul de Souza, Karim Fizazi, Paul Mainwaring, Josep M Piulats, Siobhan Ng, Joan Carles, Peter F A Mulders, Ethan Basch, Eric J Small, Fred Saad, Dirk Schrijvers, Hendrik Van Poppel, Som D Mukherjee, Henrik Suttmann, Winald R Gerritsen, Thomas W Flaig, Daniel J George, Evan Y Yu, Eleni Efstathiou, Allan Pantuck, Eric Winquist, Celestia S Higano, Mary-Ellen Taplin, Youn Park, Thian Kheoh, Thomas Griffin, Howard I Scher, Dana E Rathkopf; COU-AA-302 Investigators
Collaborators, Affiliations
Randomized Controlled Trial

Abiraterone in metastatic prostate cancer without previous chemotherapy

Charles J Ryan et al. N Engl J Med. .

Erratum in

  • N Engl J Med. 2013 Feb 7;368(6):584

Abstract

Background: Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after chemotherapy. We evaluated this agent in patients who had not received previous chemotherapy.

Methods: In this double-blind study, we randomly assigned 1088 patients to receive abiraterone acetate (1000 mg) plus prednisone (5 mg twice daily) or placebo plus prednisone. The coprimary end points were radiographic progression-free survival and overall survival.

Results: The study was unblinded after a planned interim analysis that was performed after 43% of the expected deaths had occurred. The median radiographic progression-free survival was 16.5 months with abiraterone-prednisone and 8.3 months with prednisone alone (hazard ratio for abiraterone-prednisone vs. prednisone alone, 0.53; 95% confidence interval [CI], 0.45 to 0.62; P<0.001). Over a median follow-up period of 22.2 months, overall survival was improved with abiraterone-prednisone (median not reached, vs. 27.2 months for prednisone alone; hazard ratio, 0.75; 95% CI, 0.61 to 0.93; P=0.01) but did not cross the efficacy boundary. Abiraterone-prednisone showed superiority over prednisone alone with respect to time to initiation of cytotoxic chemotherapy, opiate use for cancer-related pain, prostate-specific antigen progression, and decline in performance status. Grade 3 or 4 mineralocorticoid-related adverse events and abnormalities on liver-function testing were more common with abiraterone-prednisone.

Conclusions: Abiraterone improved radiographic progression-free survival, showed a trend toward improved overall survival, and significantly delayed clinical decline and initiation of chemotherapy in patients with metastatic castration-resistant prostate cancer. (Funded by Janssen Research and Development, formerly Cougar Biotechnology; ClinicalTrials.gov number, NCT00887198.).

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Figures

Figure 1
Figure 1. Kaplan-Meier Estimates of Radiographic Progression-Free Survival and Overall Survival and Forest Plots by Subgroup
A. Radiographic Progression-free Survival B. Radiographic Progression-free Survival in Prespecified Subgroups. ALK-P denotes alkaline phosphatase; BPI, Brief Pain Inventory; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; LDH, lactate dehydrogenase; NE, not evaluable; PSA, prostate-specific antigen. Note: Hazard ratio is based on a nonstratified proportional hazards model C. Overall Survival D. Overall Survival in Prespecified Subgroups. Abbreviations as in panel B.
Figure 1
Figure 1. Kaplan-Meier Estimates of Radiographic Progression-Free Survival and Overall Survival and Forest Plots by Subgroup
A. Radiographic Progression-free Survival B. Radiographic Progression-free Survival in Prespecified Subgroups. ALK-P denotes alkaline phosphatase; BPI, Brief Pain Inventory; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; LDH, lactate dehydrogenase; NE, not evaluable; PSA, prostate-specific antigen. Note: Hazard ratio is based on a nonstratified proportional hazards model C. Overall Survival D. Overall Survival in Prespecified Subgroups. Abbreviations as in panel B.
Figure 1
Figure 1. Kaplan-Meier Estimates of Radiographic Progression-Free Survival and Overall Survival and Forest Plots by Subgroup
A. Radiographic Progression-free Survival B. Radiographic Progression-free Survival in Prespecified Subgroups. ALK-P denotes alkaline phosphatase; BPI, Brief Pain Inventory; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; LDH, lactate dehydrogenase; NE, not evaluable; PSA, prostate-specific antigen. Note: Hazard ratio is based on a nonstratified proportional hazards model C. Overall Survival D. Overall Survival in Prespecified Subgroups. Abbreviations as in panel B.
Figure 1
Figure 1. Kaplan-Meier Estimates of Radiographic Progression-Free Survival and Overall Survival and Forest Plots by Subgroup
A. Radiographic Progression-free Survival B. Radiographic Progression-free Survival in Prespecified Subgroups. ALK-P denotes alkaline phosphatase; BPI, Brief Pain Inventory; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; LDH, lactate dehydrogenase; NE, not evaluable; PSA, prostate-specific antigen. Note: Hazard ratio is based on a nonstratified proportional hazards model C. Overall Survival D. Overall Survival in Prespecified Subgroups. Abbreviations as in panel B.
Figure 2.
Figure 2.. Secondary Exploratory Efficacy End Points
A. Time to Deterioration in Eastern Cooperative Oncology Group Performance Status Score by ≥1 Grade B. Time to Initiation of Cytotoxic Chemotherapy C. Time to Opiate Use for Prostate Cancer Pain D. Time to Prostate-specific Antigen Progression
Figure 2.
Figure 2.. Secondary Exploratory Efficacy End Points
A. Time to Deterioration in Eastern Cooperative Oncology Group Performance Status Score by ≥1 Grade B. Time to Initiation of Cytotoxic Chemotherapy C. Time to Opiate Use for Prostate Cancer Pain D. Time to Prostate-specific Antigen Progression
Figure 2.
Figure 2.. Secondary Exploratory Efficacy End Points
A. Time to Deterioration in Eastern Cooperative Oncology Group Performance Status Score by ≥1 Grade B. Time to Initiation of Cytotoxic Chemotherapy C. Time to Opiate Use for Prostate Cancer Pain D. Time to Prostate-specific Antigen Progression
Figure 2.
Figure 2.. Secondary Exploratory Efficacy End Points
A. Time to Deterioration in Eastern Cooperative Oncology Group Performance Status Score by ≥1 Grade B. Time to Initiation of Cytotoxic Chemotherapy C. Time to Opiate Use for Prostate Cancer Pain D. Time to Prostate-specific Antigen Progression
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