Comparative analysis of the effectiveness of abiraterone before and after docetaxel in patients with metastatic castration-resistant prostate cancer

Table 1 Characteristics of randomized controlled trials included in the meta-analysis

Clinical trial characteristics	COU-AA-302[15]	COU-AA-301[14]
Inclusion criteria	(1) Age ≥ 18 yr; (2) Confirmed metastatic disease; (3) Histologically or cytologically confirmed Prostate Adeno-CA; (4) PSA progression (PCWG2) or radiograph progression w/ or w/o PSA progression; (5) Testosterone < 50 ng/dL; (6) ECOG 0 or 1; (7) BPI-SF 0-3	(1) Confirmed metastatic disease; (2) Histologically or cytologically confirmed Prostate Adeno-CA; (3) PSA progression (PCWG2) or radiograph progression w/ or w/o PSA progression; (4) Testosterone < 50 ng/dL; (5) ECOG ≤ 2; (6) previous therapy with docetaxel
Exclusion criteria	(1) Visceral metastasis; (2) Previous use of ketoconazole lasting > 7 d	(1) Elevated LFT (> 2.5 ULN) (2) Previous ketoconazole therapy; (3) Viral hepatitis; (4) Chronic liver disease; (5) Uncontrolled HTN; (6) Pituitary or adrenal dysfunction
Eligible patients	546 (abiraterone vs control)	797
Study arm medication and dose	Abiraterone Acetate 1 gm OD + Prednisone 5 mg BID
Jadad Score	4	5
Median overall survival: Abiraterone vs Placebo (mo)	Not reached vs 27.2	15.8 vs 11.2
Median time to PSA PFS: Abiraterone vs Placebo (mo)	11.1 vs 5.6	8.5 vs 6.6
Median time to Radiographic PFS: Abiraterone vs Placebo (mo)	16.5 vs 8.3	5.6 vs 3.6
Median follow up time: Abiraterone vs Placebo (mo)	22.2	12.8

PCWG2: Prostate Cancer Working Group 2 Criteria; PSA: Prostate-specific antigen; BPR-SF: Brief pain inventory-short form; ECOG: Eastern Cooperative Oncology Criteria; HTN: Hypertension; ULN: Upper limit of normal range; w/o: With/without; PFS: Progression free survival; OD: Once daily; BID: Twice daily; Adeno-CA: Adenocarcinoma.

Table 2 Rates of tumor response attributable to abiraterone in the pre- and post-chemotherapy settings

	Pre-chemotherapyrate (95%CI)	Post-chemotherapyrate (95%CI)
Objective response	20.0% (16.9%-23.6%)	11.5% (9.5%-13.9%)b
PSA response	38.0% (34.0%-42.1%)	24.0% (21.2%-27.1%)b

^bP < 0.01, pre-chemotherapy vs post-chemotherapy rates. The response rate attributable to abiraterone = rate of abiraterone and prednisone minus that of placebo and prednisone.

Table 3 Incidence of adverse events attributable to abiraterone in the pre- and post-chemotherapy settings

Adverse events	Pre-chemotherapyincidence (95%CI)	Post-chemotherapyincidence (95%CI)
Cardiac disorders all-grade	3.0% (1.9%-4.8%)	4.0% (2.8%-5.6%)
Fluid retention and edema all-grade	4.0% (2.6%-6.0%)	9.0% (7.2%-11.2%)b
Hypertension all-grade	9.0% (6.9%-11.7%)	3.0% (2.0%-4.4%)b
Hypokalemia all-grade	9.0% (7.2%-11.2%)	4.0% (2.6%-6.0%)b
Hypokalemia high-grade	0.1% (1.0%-1.5%)	3.7% (2.6%-5.2%)b

^bP < 0.01, pre-chemotherapy vs post-chemotherapyincidence. The incidence rate attributable to abiraterone = incidence rate of abiraterone and prednisone minus that of placebo and prednisone.