Abiraterone in Metastatic Prostate Cancer without Previous Chemotherapy

被引：2362

作者：

Ryan, Charles J. ^{[1
]}

Smith, Matthew R. ^{[2
]}

de Bono, Johann S. ^{[4
,5
]}

Molina, Arturo ^{[6
]}

Logothetis, Christopher J. ^{[8
]}

de Souza, Paul ^{[9
]}

Fizazi, Karim ^{[12
]}

Mainwaring, Paul ^{[10
]}

Piulats, Josep M. ^{[13
]}

Ng, Siobhan ^{[11
]}

Carles, Joan ^{[14
]}

Mulders, Peter F. A. ^{[15
]}

Basch, Ethan ^{[17
]}

Small, Eric J. ^{[1
]}

Saad, Fred ^{[18
]}

Schrijvers, Dirk ^{[21
]}

Van Poppel, Hendrik ^{[22
]}

Mukherjee, Som D. ^{[19
]}

Suttmann, Henrik ^{[23
]}

Gerritsen, Winald R. ^{[16
]}

Flaig, Thomas W. ^{[24
]}

George, Daniel J. ^{[25
]}

Yu, Evan Y. ^{[26
]}

Efstathiou, Eleni ^{[8
,27
]}

Pantuck, Allan ^{[7
]}

Winquist, Eric ^{[20
]}

Higano, Celestia S. ^{[26
]}

Taplin, Mary-Ellen ^{[3
]}

Park, Youn ^{[6
]}

Kheoh, Thian ^{[6
]}

Griffin, Thomas ^{[6
]}

Scher, Howard I. ^{[17
]}

Rathkopf, Dana E. ^{[17
]}

机构：

[1] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA

[2] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA

[3] Dana Farber Canc Inst, Boston, MA 02115 USA

[4] Inst Canc Res, Sutton, Surrey, England

[5] Royal Marsden Hosp, Sutton, Surrey, England

[6] Janssen Res & Dev, Los Angeles, CA USA

[7] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA

[8] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[9] St George Private Hosp, Kogarah, NSW, Australia

[10] Haematol & Oncol Clin Australia, Brisbane, Qld, Australia

[11] St John God Hosp, Subiaco, WA, Australia

[12] Univ Paris 11, Inst Gustave Roussy, Villejuif, France

[13] Inst Catala Oncol Hosp, Barcelona, Spain

[14] Univ Vall dHebron, Barcelona, Spain

[15] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands

[16] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands

[17] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA

[18] Univ Montreal, Montreal, PQ, Canada

[19] Juravinski Canc Ctr, Hamilton Hlth Serv, Hamilton, ON, Canada

[20] London Hlth Sci Ctr, London, ON, Canada

[21] Hosp Network Antwerp ZNA Middelheim, Antwerp, Belgium

[22] Katholieke Univ Leuven Hosp, Louvain, Belgium

[23] Urologikum Hamburg, Hamburg, Germany

[24] Univ Colorado, Ctr Canc, Aurora, CO USA

[25] Duke Univ Hosp, Med Ctr, Durham, NC USA

[26] Univ Washington, Seattle, WA 98195 USA

[27] Univ Athens, Sch Med, Alexandra Hosp, Dept Clin Therapeut, GR-10679 Athens, Greece

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2013年 / 368卷 / 02期

关键词：

HUMAN CYTOCHROME P450(17-ALPHA); HORMONAL-THERAPY; CONTROLLED-TRIAL; END-POINTS; ACETATE; MITOXANTRONE; INHIBITION; PREDNISONE; DOCETAXEL; CYP17;

D O I：

10.1056/NEJMoa1209096

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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.)

引用

页码：138 / 148

页数：11

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