Updated Interim Efficacy Analysis and Long-term Safety of Abiraterone Acetate in Metastatic Castration-resistant Prostate Cancer Patients Without Prior Chemotherapy (COU-AA-302)

• Published in: European urology Vol. 66; no. 5; pp. 815 - 825
• Main Authors: Rathkopf, Dana E., Smith, Matthew R., de Bono, Johann S., Logothetis, Christopher J., Shore, Neal D., de Souza, Paul, Fizazi, Karim, Mulders, Peter F.A., Mainwaring, Paul, Hainsworth, John D., Beer, Tomasz M., North, Scott, Fradet, Yves, Van Poppel, Hendrik, Carles, Joan, Flaig, Thomas W., Efstathiou, Eleni, Yu, Evan Y., Higano, Celestia S., Taplin, Mary-Ellen, Griffin, Thomas W., Todd, Mary B., Yu, Margaret K., Park, Youn C., Kheoh, Thian, Small, Eric J., Scher, Howard I., Molina, Arturo, Ryan, Charles J., Saad, Fred
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01.11.2014; Elsevier
• Subjects: Abiraterone Acetate; Aged; Androstenes - administration & dosage; Androstenes - adverse effects; Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Agents, Hormonal - adverse effects; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Chemotherapy-naive; Cytochrome P-450 Enzyme Inhibitors - administration & dosage; Cytochrome P-450 Enzyme Inhibitors - adverse effects; Disease Progression; Disease-Free Survival; Double-Blind Method; Drug Administration Schedule; Efficacy; Gynecology. Andrology. Obstetrics; Humans; Kaplan-Meier Estimate; Male; Male genital diseases; Medical sciences; Metastatic castration-resistant prostate cancer; Middle Aged; Neoplasm Metastasis; Neoplasms, Hormone-Dependent - drug therapy; Neoplasms, Hormone-Dependent - enzymology; Neoplasms, Hormone-Dependent - mortality; Neoplasms, Hormone-Dependent - pathology; Nephrology. Urinary tract diseases; Prednisone - administration & dosage; Proportional Hazards Models; Prostatic Neoplasms, Castration-Resistant - drug therapy; Prostatic Neoplasms, Castration-Resistant - enzymology; Prostatic Neoplasms, Castration-Resistant - mortality; Prostatic Neoplasms, Castration-Resistant - pathology; Risk Factors; Safety; Steroid 17-alpha-Hydroxylase - antagonists & inhibitors; Steroid 17-alpha-Hydroxylase - metabolism; Time Factors; Treatment Outcome; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Urology; Chemotherapy-naive; Efficacy; Safety; Metastatic castration-resistant prostate cancer; Abiraterone acetate; Nephrology; Prostate disease; Toxicity; Antihormone; Metastasis; Urology; Castration; Advanced stage; Male genital diseases; Human; Urinary system disease; Abiraterone; Treatment efficiency; Antiandrogen; Malignant tumor; Acetate; Long term; Resistance; Chemotherapy; Treatment; Metastatic; Prostate cancer; Cancer
• ISSN: 0302-2838; 1873-7560; 1873-7560
• DOI: 10.1016/j.eururo.2014.02.056

Abiraterone acetate (an androgen biosynthesis inhibitor) plus prednisone is approved for treating patients with metastatic castration-resistant prostate cancer (mCRPC). Study COU-AA-302 evaluated abiraterone acetate plus prednisone versus prednisone alone in mildly symptomatic or asymptomatic patients with progressive mCRPC without prior chemotherapy. Report the prespecified third interim analysis (IA) of efficacy and safety outcomes in study COU-AA-302. Study COU-AA-302, a double-blind placebo-controlled study, enrolled patients with mCRPC from April 2009 to June 2010. A total of 1088 patients were stratified by Eastern Cooperative Oncology Group performance status (0 vs 1). Patients were randomised 1:1 to abiraterone 1000mg plus prednisone 5mg twice daily by mouth versus prednisone. Co–primary end points were radiographic progression-free survival (rPFS) and overall survival (OS). Median times to event outcomes were estimated using the Kaplan-Meier method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were derived using the Cox model, and treatment comparison used the log-rank test. The O’Brien-Fleming Lan-DeMets α-spending function was used for OS. Adverse events were summarised descriptively. With a median follow-up duration of 27.1 mo, improvement in rPFS was statistically significant with abiraterone treatment versus prednisone (median: 16.5 vs 8.2 mo; HR: 0.52 [95% CI, 0.45–0.61]; p<0.0001). Abiraterone improved OS (median: 35.3 vs 30.1 mo; HR: 0.79 [95% CI, 0.66–0.95]; p=0.0151) but did not reach the prespecified statistical efficacy boundary (α-level: 0.0035). A post hoc multivariate analysis for OS using known prognostic factors supported the primary results (HR: 0.74 [95% CI, 0.61–0.89]; p=0.0017), and all clinically relevant secondary end points and patient-reported outcomes improved. While the post hoc nature of the long-term safety analysis is a limitation, the safety profile with longer treatment exposure was consistent with prior reports. The updated IA of study COU-AA-302 in patients with mCRPC without prior chemotherapy confirms that abiraterone delays disease progression, pain, and functional deterioration and has clinical benefit with a favourable safety profile, including in patients treated for ≥24 mo. Study COU-AA-302, ClinicalTrials.gov number, NCT00887198. The updated results of this ongoing study showed that disease progression was delayed in patients with advanced prostate cancer who were treated with abiraterone acetate and prednisone, and there was a continued trend in prolongation of life compared with patients treated with prednisone alone. Treatment with abiraterone acetate and prednisone was well tolerated by patients who were treated for >2 yr. The updated analysis of study COU-AA-302 confirms the continued clinical benefit of abiraterone acetate and prednisone in the treatment of chemotherapy-naive patients with metastatic castration-resistant prostate cancer. Long-term use of abiraterone and prednisone for ≥24 mo was not associated with any new safety concerns.