Abiraterone and Increased Survival in Metastatic Prostate Cancer

By J. D. de Bono, C. Logothetis, A. Molina, K. Fizazi, S. North, L. Chu, K. Chi, Robert J. Jones, O. Goodman, F. Saad and 22 more. New England Journal of Medicine, 2011

4,290 citations recorded by the source corpus.

BACKGROUND Biosynthesis of extragonadal androgen may contribute to the progression of castration-resistant prostate cancer. We evaluated whether abiraterone acetate, an inhibitor of androgen biosynthesis, prolongs overall survival among patients with metastatic castration-resistant prostate cancer who have received chemotherapy. METHODS We randomly assigned, in a 2:1 ratio, 1195 patients who had previously received docetaxel to receive 5 mg of prednisone twice daily with either 1000 mg of abiraterone acetate (797 patients) or placebo (398 patients). The primary end point was overall survival. The secondary end points included time to prostate-specific antigen (PSA) progression (elevation in the PSA level according to prespecified criteria), progression-free survival according to radiologic findings based on prespecified criteria, and the PSA response rate. RESULTS After a median follow-up of 12.8 months, overall survival was longer in the abiraterone acetate–prednisone group than in the placebo–prednisone group (14.8 months vs. 10.9 months; hazard ratio, 0.65; 95% confidence interval, 0.54 to 0.77; P<0.001). Data were unblinded at the interim analysis, since these results exceeded the preplanned criteria for study termination. All secondary end points, including time to PSA progression (10.2 vs. 6.6 months; P<0.001), progression-free survival (5.6 months vs. 3.6 months; P<0.001), and PSA response rate (29% vs. 6%, P<0.001), favored the treatment group. Mineralocorticoid-related adverse events, including fluid retention, hypertension, and hypokalemia, were more frequently reported in the abiraterone acetate–prednisone group than in the placebo–prednisone group. CONCLUSIONS The inhibition of androgen biosynthesis by abiraterone acetate prolonged overall survival among patients with metastatic castration-resistant prostate cancer who previously received chemotherapy. (Funded by Cougar Biotechnology; COU-AA-301 ClinicalTrials.gov number, NCT00638690.)

Subfields: Cancer Research, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/ccbbe4c8cc306a9a781519792b386f3bfd05a506

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. M. Hallek
2. Hans Clevers
3. C. Sawyers
4. R. DePinho

In Pulmonary and Respiratory Medicine

1. John Wongvipat
2. C. Sawyers
3. M. Hallek
4. R. Vessella
5. Mark A. Rubin
6. A. Heidenreich
7. Michel Bolla
8. N. Mottet

Citations in the corpus

• ARN-509: a novel anti-androgen for prostate cancer treatment (2012, neutral): “9 months over control (prednisone only) in CRPC patients previously treated with docetaxel (8).”
• Glucocorticoid Receptor Confers Resistance to Anti-Androgens by Bypassing Androgen Receptor Blockade (2013, neutral): “Recently approved drugs that target androgen receptor (AR) signaling such as abiraterone and enzalutamide have rapidly become standard therapies for advanced-stage prostate cancer (Scher et al., 2012; de Bono et al., 2011).”
• Organoid cultures derived from patients with advanced prostate cancer (2014, positive): “These include the next-generation antiandrogen enzalutamide and the androgen synthesis inhibitor abiraterone acetate, both of which have been shown to significantly prolong life (de Bono et al., 2011; Ryan et al., 2012; Scher et al., 2012).”
• Abiraterone plus Prednisone in Metastatic, Castration‐Sensitive Prostate Cancer (2017, neutral): “Back pain 110 (18) 14 (2) 0 123 (20) 19 (3) 0”
• Androgen Receptor Pathway-Independent Prostate Cancer Is Sustained through FGF Signaling (2017, background): “Several drugs, including improved AR antagonists and inhibitors of androgen synthesis, extend survival (de Bono et al., 2011; Scher et al., 2012), although to date complete remissions have been rare.”
• Genetics and biology of prostate cancer (2018, background): “Abiraterone, a CYP17A1 inhibitor that blocks androgen production, also improves survival of patients with advanced prostate cancer with or without prior chemotherapy (de Bono et al. 2011; Ryan et al. 2013; Fizazi et al. 2017; James et al. 2017).”
• Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy (2017, neutral): “(%) No 50 (5) 61 (6) Short‐term antiandrogen 902 (94) 895 (93) Long‐term antiandrogen 5 (1) 4 (<1) Radiotherapy planned — no.”
• Resistance to CYP17A1 inhibition with abiraterone in castration resistant prostate cancer: Induction of steroidogenesis and androgen receptor splice variants (2011, neutral): “Clin Cancer Res; 17(18) September 15, 2011 Clinical Cancer Research 5920”
• Prostate Cancer (2018, background): “The inhibitors of 5-alpha-reductase, i.e. finasteride and dutasteride, reduce the risk for prostate cancer by 20-25%, see Prostate Cancer Study Results.”
• A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). (2015, background): “77) 4 [49]”