Abiraterone Acetate Prolongs Survival in Metastatic Prostate Cancer

The final analysis of a phase III trial shows that metastatic prostate cancer patients given abiraterone acetate plus prednisone have significantly longer overall survival than those given prednisone plus placebo

medwireNews: Abiraterone acetate plus prednisone treatment significantly extends survival in men with metastatic, castration-resistant prostate cancer compared with prednisone alone, research shows.

Charles Ryan, from University of California San Francisco in the USA, and colleagues report the findings of the final analysis of the phase III COU-AA-302 trial in The Lancet Oncology.

After a median follow-up of 49.2 months, median overall survival (OS) was 34.7 months for the 546 chemotherapy-naive prostate cancer patients who were randomly assigned to receive abiraterone acetate plus prednisone. This was significantly longer than the median OS of 30.3 months for the 542 participants who received placebo plus prednisone.

The mortality risk was significantly lower for patients given abiraterone acetate plus prednisone than for those who received prednisone alone, at a hazard ratio (HR) of 0.81. This difference between the groups remained after adjusting for the patients in the placebo group who crossed over as per protocol to receive the experimental treatment, at an HR of 0.74.

Additionally, the median time to opiate use for prostate cancer-associated pain was significantly delayed in the abiraterone acetate versus the placebo group, at 33.4 versus 23.4 months.

Cardiac disorders, elevated alanine aminotransferase and hypertension were the most frequent relevant grade 3 or higher toxicities, occurring in 8% versus 4%, 6% versus less than 1% and 5% versus 3% of men in the abiraterone acetate and placebo arms, respectively.

The researchers say that the toxicity findings are consistent with those at previous interim analyses and further support the “favourable safety profile” of the drug, even after extended follow-up.

Previously reported radiographical progression-free survival results have been sufficient for abiraterone acetate to gain regulatory approval in several countries, comment Charles J Ryan et al, adding that their data “emphasise the importance of continuing data collection and prespecified final analyses in clinical trials”.

In a linked commentary, Ravi Madan and William Dahut, from the National Cancer Institute in Bethesda, Maryland, USA, point out that the “remarkable” OS findings are likely an underestimate, given that 44% of men in the placebo group were ultimately treated with abiraterone acetate.

They conclude: “Fuelled by the remarkable revolution in therapies for metastatic castration-resistant prostate cancer, a new generation of clinical trials should bring these therapeutic advances to bear on the tumour when it is localised, with hopes of downstaging the disease before radiation or surgery.

“We should no longer settle for shifting Kaplan–Meier curves in metastatic prostate cancer; instead, we should focus on finding ways to shift paradigms by using these therapies to enhance cure rates at diagnosis.”


Ryan CJ, Smith MR, Fizazi K, et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 2015; Online First 15 January. doi:10.1016/S1470-2045(14)71205-7

Madan R, Dahut WL. Abiraterone’s efficacy confirmed; time to aim higher. Lancet Oncol 2015; Online First 15 January. doi:10.1016/S1470-2045(15)70005-7

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