COU-AA-301: trial | Bending the Curve: Trial by Trial

COU-AA-301

Abiraterone and increased survival in metastatic prostate cancer

Population

Men with metastatic castration-resistant prostate cancer that had progressed after docetaxel

Design

Randomized (2:1), double-blind, placebo-controlled phase 3 trial: abiraterone acetate 1000 mg once daily plus prednisone 5 mg twice daily versus placebo plus prednisone. Stratified by ECOG performance status, pain, number of previous chemotherapy regimens and type of progression.

Primary endpoint

Arms

Placebo plus prednisone (control, n = 398): Placebo plus prednisone 5 mg twice daily
Abiraterone acetate plus prednisone (experimental, n = 797): Abiraterone acetate 1000 mg once daily plus prednisone 5 mg twice daily

People

de Bono JS, COU-AA-301 Investigators

OSHR 0.65 (95% CI 0.54–0.77)Δ median OS+3.9 monthsOSHR 0.74 (95% CI 0.64–0.86)Δ median OS+4.6 monthsrPFSHR 0.66 (95% CI 0.58–0.76)Δ median rPFS+2 months

Show the numbers

Results reported for COU-AA-301
Endpoint	Analysis	Abiraterone acetate plus prednisone	Placebo plus prednisone	Effect
OSRandomized patients (analysis population not stated in the NEJM abstract)	interimmedian follow-up 12.8 monthsde 2011	median 14.8 months	median 10.9 months	HR 0.65 (95% CI 0.54–0.77)P<0.001Preplanned interim analysis; data were unblinded because the results exceeded the criteria for study termination.
OS	finalmedian follow-up 20.2 monthsFizazi 2012	median 15.8 months (14.8–17.0)	median 11.2 months (10.4–13.1)	HR 0.74 (95% CI 0.64–0.86)P<0.0001Final analysis before crossover from placebo to abiraterone, after 775 of the prespecified 797 deaths.
rPFS	finalmedian follow-up 20.2 monthsFizazi 2012	median 5.6 months (5.6–6.5)	median 3.6 months (2.9–5.5)	HR 0.66 (95% CI 0.58–0.76)P<0.0001Radiologic progression-free survival, a secondary end point.

Results reported for COU-AA-301
Endpoint	Analysis	Abiraterone acetate plus prednisone	Placebo plus prednisone	Effect
OSRandomized patients (analysis population not stated in the NEJM abstract)	interimmedian follow-up 12.8 monthsde 2011	median 14.8 months	median 10.9 months	HR 0.65 (95% CI 0.54–0.77)P<0.001Preplanned interim analysis; data were unblinded because the results exceeded the criteria for study termination.
OS	finalmedian follow-up 20.2 monthsFizazi 2012	median 15.8 months (14.8–17.0)	median 11.2 months (10.4–13.1)	HR 0.74 (95% CI 0.64–0.86)P<0.0001Final analysis before crossover from placebo to abiraterone, after 775 of the prespecified 797 deaths.
rPFS	finalmedian follow-up 20.2 monthsFizazi 2012	median 5.6 months (5.6–6.5)	median 3.6 months (2.9–5.5)	HR 0.66 (95% CI 0.58–0.76)P<0.0001Radiologic progression-free survival, a secondary end point.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
OS	0.65	0.54–0.77
OS	0.74	0.64–0.86
rPFS	0.66	0.58–0.76

Illustrative — modelled from reported values, not trial data. OS, interim.

Show curves

Placebo plus prednisone (control)
Abiraterone acetate plus prednisone (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Placebo plus prednisone	Abiraterone acetate plus prednisone
0	100.0%	100.0%
9	56.4%	65.6%
19	29.9%	41.1%
28	16.9%	26.9%
37	9.5%	17.7%

Illustrative — modelled from reported values, not trial data. OS, final.

Show curves

Placebo plus prednisone (control)
Abiraterone acetate plus prednisone (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Placebo plus prednisone	Abiraterone acetate plus prednisone
0	100.0%	100.0%
10	53.9%	64.5%
20	29.0%	41.6%
30	15.6%	26.8%
40	8.4%	17.3%

Appears in

2011 Abiraterone after docetaxel improves survival (COU-AA-301)

Sources

de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364(21):1995-2005.
PubMed DOI
Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012;13(10):983-92.
PubMed DOI