Abiraterone acetate in patients with metastatic castration-resistant prostate cancer: long term outcome of the Temporary Authorization for Use programme in France

Abstract

BackgroundCOU-AA-301 trial has proved that abiraterone acetate (AA), a selective inhibitor of androgen biosynthesis, improved overall survival (OS) of patients with metastatic castration resistant prostate cancer (mCRPC) after a first line of docetaxel. Based on this result, a Temporary Authorization for Use (TAU) was performed between December 2010 and July 2011 to provide patients with mCRPC the opportunity to receive AA before its commercialization. The aim of this study was to evaluate safety and efficacy of AA treatment in this TAU.MethodsBetween December 2010 and July 2011, we conducted an ambispective, multicentric cohort study and investigated data from 20 centres participating to the AA TAU for patients presenting mCRPC and already treated by a first line of chemotherapy (CT). Statistical analyses of the data were performed using the Stata software v13 to identify predictive and prognostic factors.ResultsAmong the 408 patients, 306 were eligible with a follow-up at 3 years. Median OS was 37.1 months from beginning of CT and 14.6 months from AA introduction. 211 patients (69%) received ≥ 3 months of AA and 95 patients (31%) were treated less than 3 months. In the multivariate analyses, duration of AA was significantly correlated with PSA decrease at 3 months. Additionally, shorter time under AA treatment, presence of multiple sites of metastasis and previous hormonal treatment duration were three independent factors associated with poorer OS. At the time of analysis ten patients were still under treatment for more than 3 years.ConclusionsBiochemical response monitored by PSA changes at 3 months is a strong predictive factor for AA treatment duration. Some high responders’ patients could beneficiate from AA for more than 3 years.

Predictors of long-term response to abiraterone in patients with metastastic castration-resistant prostate cancer: a retrospective cohort study

“…Retrospective analysis of the Temporary Authorization for Use programme in France showed that PSA decrease at 3 months was a predictive factor for abiraterone treatment duration [24]. In our experience we could not explore this correlation because of different timepoints for PSA evaluation.…”

“…Similarly, time to CRPC ≥12 months and ECOG-PS score 0-1 were associated with improved PFS in a cohort of 173 patients treated with enzalutamide, abiraterone or other hormonal therapies at two French cancer centers [14]. The duration of previous hormonal therapy resulted to be associated with better OS also in the abiraterone-treated cohort (n=306) of the aforementioned Temporary Authorization for Use study [24]. Furthermore, time to development of CRPC was identified as the strongest predictor of PSA response, PSA-PFS and OS also when AR-targeted therapies were used in a second line setting, as reported in a retrospective study evaluating the outcome of 126 patients treated with sequential abiraterone and enzalutamide [25].…”

Consensus statements on the management of metastatic prostate cancer from the Hong Kong Urological Association and Hong Kong Society of Uro‐Oncology

“…In an observational study , patients with mCRPC with a higher Gleason score had a lower chance of being responsive to abiraterone. By contrast, the survival benefit gained with docetaxel in the TAX 327 trial was most pronounced in patients with a higher Gleason score (i.e.…”

Low-dose docetaxel, estramustine and prednisolone combination chemotherapy for castration-resistant prostate cancer

“…If patients with CRPC have developed early resistance to ADT, DOC should be used early during the course of treatment. Houédé et al (16) reported that patients with a high Gleason score (8-10) tended to respond poorly to abiraterone. Similarly, it was reported that patients with poorly differentiated cancers (Gleason score 8-10) benefit the most from DOC use (17).…”