Abiraterone (Page 9 of 12)

Table 7: Overall Survival of Patients Treated with Either Abiraterone Acetate or Placebo in Combination with Prednisone in COU-AA-301 (Intent-to-Treat Analysis)

Abiraterone Acetate with Placebo with
Prednisone Prednisone
( N=797) ( N=398)
Primary Survival Analysis
Deaths (%) 333 (42%) 219 (55%)
Median survival (months) 14.8 (14.1, 15.4) 10.9 (10.2, 12.0)
(95% CI)
p-value 1 <0.0001
Hazard ratio (95% CI) 2 0.646 (0.543, 0.768)
Updated Survival Analysis
Deaths (%) 501 (63%) 274 (69%)
Median survival (months) 15.8 (14.8, 17.0) 11.2 (10.4, 13.1)
(95% CI)
Hazard ratio (95% CI) 2 0.740 (0.638, 0.859)

1 p-value is derived from a log-rank test stratified by ECOG performance status score (0-1 vs. 2), pain score (absent vs. present), number of prior chemotherapy regimens (1 vs. 2), and type of disease progression (PSA only vs. radiographic).

2 Hazard Ratio is derived from a stratified proportional hazards model. Hazard ratio <1 favors abiraterone acetate with prednisone.

Figure 1: Kaplan-Meier Overall Survival Curves in COU-AA-301 (Intent-to-Treat Analysis)

Figure 1
(click image for full-size original)

COU-AA-302: Patients with metastatic CRPC who had not received prior cytotoxic chemotherapy

In COU-AA-302, (NCT00887198), 1088 patients were randomized 1:1 to receive either abiraterone acetate orally at a dose of 1,000 mg once daily (N=546) or Placebo orally once daily (N=542). Both arms were given concomitant prednisone 5 mg twice daily. Patients continued treatment until radiographic or clinical (cytotoxic chemotherapy, radiation or surgical treatment for cancer, pain requiring chronic opioids, or ECOG performance status decline to 3 or more) disease progression, unacceptable toxicity or withdrawal. Patients with moderate or severe pain, opiate use for cancer pain, or visceral organ metastases were excluded.

Patient demographics were balanced between the treatment arms. The median age was 70 years. The racial distribution of patients treated with abiraterone acetate was 95% Caucasian, 2.8% Black, 0.7% Asian and 1.1% Other. The ECOG performance status was 0 for 76% of patients, and 1 for 24% of patients. Co-primary efficacy endpoints were overall survival and radiographic progression-free survival (rPFS). Baseline pain assessment was 0–1 (asymptomatic) in 66% of patients and 2–3 (mildly symptomatic) in 26% of patients as defined by the Brief Pain Inventory-Short Form (worst pain over the last 24 hours).

Radiographic progression-free survival was assessed with the use of sequential imaging studies and was defined by bone scan identification of 2 or more new bone lesions with confirmation (Prostate Cancer Working Group 2 criteria) and/or modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria for progression of soft tissue lesions. Analysis of rPFS utilized centrally-reviewed radiographic assessment of progression.

The planned final analysis for OS, conducted after 741 deaths (median follow up of 49 months) demonstrated a statistically significant OS improvement in patients treated with abiraterone acetate with prednisone compared to those treated with placebo with prednisone (Table 8 and Figure 2). Sixty-five percent of patients on the abiraterone acetate arm and 78% of patients on the placebo arm used subsequent therapies that may prolong OS in metastatic CRPC. Abiraterone acetate was used as a subsequent therapy in 13% of patients on the abiraterone acetate arm and 44% of patients on the placebo arm.

Table 8: Overall Survival of Patients Treated with Either Abiraterone Acetate or Placebo in Combination with Prednisone in COU-AA-302 (Intent-to-Treat Analysis)

Overall Survival Abiraterone Acetate with Prednisone (N=546) Placebo with Prednisone (N=542)
Deaths 354 (65%) 387 (71%)
Median survival (months) (95% CI) 34.7 (32.7, 36.8) 30.3 (28.7, 33.3)
p-value 1 0.0033
Hazard ratio 2 (95% CI) 0.81 (0.70, 0.93)

1 p-value is derived from a log-rank test stratified by ECOG performance status score (0 vs. 1). 2 Hazard Ratio is derived from a stratified proportional hazards model. Hazard ratio <1 favors abiraterone acetate with prednisone.

Figure 2: Kaplan Meier Overall Survival Curves in COU-AA-302

Figure 2
(click image for full-size original)

At the pre-specified rPFS analysis, 150 (28%) patients treated with abiraterone acetate with prednisone and 251 (46%) patients treated with placebo with prednisone had radiographic progression. A significant difference in rPFS between treatment groups was observed (Table 9 and Figure 3).

Table 9: Radiographic Progression-free Survival of Patients Treated with Either Abiraterone Acetate or Placebo in Combination with Prednisone in COU-AA-302 (Intent-to-Treat Analysis)

Radiographic Progression-free Survival Abiraterone Acetate with Prednisone (N=546) Placebo with Prednisone (N=542)
Progression or death 150 (28%) 251 (46%)
Median rPFS (months) (95% CI) NR (11.66, NR) 8.28 (8.12, 8.54)
p-value 1 <0.0001
Hazard ratio 2 (95% CI) 0.425 (0.347, 0.522)

NR=Not reached. 1 p-value is derived from a log-rank test stratified by ECOG performance status score (0 vs. 1). 2 Hazard Ratio is derived from a stratified proportional hazards model. Hazard ratio <1 favors abiraterone acetate with prednisone.

Figure 3: Kaplan Meier Curves of Radiographic Progression-free Survival in COU-AA-302 (Intent-to-Treat Analysis)

Figure 3
(click image for full-size original)

The primary efficacy analyses are supported by the following prospectively defined endpoints. The median time to initiation of cytotoxic chemotherapy was 25.2 months for patients in the abiraterone acetate arm and 16.8 months for patients in the placebo arm (HR=0.580; 95% CI: [0.487, 0.691], p < 0.0001).

The median time to opiate use for prostate cancer pain was not reached for patients receiving abiraterone acetate and was 23.7 months for patients receiving placebo (HR=0.686; 95% CI: [0.566, 0.833], p=0.0001). The time to opiate use result was supported by a delay in patient reported pain progression favoring the abiraterone acetate arm.

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