TY - JOUR
T1 - Abiraterone acetate for patients with metastatic castration-resistant prostate cancer progressing after chemotherapy
T2 - final analysis of a multicentre, open-label, early-access protocol trial
AU - Sternberg, Cora N
AU - Castellano, Daniel
AU - Daugaard, Gedske
AU - Géczi, Lajos
AU - Hotte, Sebastien J
AU - Mainwaring, Paul N
AU - Saad, Fred
AU - Souza, Ciro
AU - Tay, Miah H
AU - Garrido, José M Tello
AU - Galli, Luca
AU - Londhe, Anil
AU - De Porre, Peter
AU - Goon, Betty
AU - Lee, Emma
AU - McGowan, Tracy
AU - Naini, Vahid
AU - Todd, Mary B
AU - Molina, Arturo
AU - George, Daniel J
AU - Abiraterone Global EAP Investigators
N1 - Copyright © 2014 Elsevier Ltd. All rights reserved.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - Background: In the final analysis of the phase 3 COU-AA-301 study, abiraterone acetate plus prednisone significantly prolonged overall survival compared with prednisone alone in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. Here, we present the final analysis of an early-access protocol trial that was initiated after completion of COU-AA-301 to enable worldwide preapproval access to abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. Methods: We did a multicentre, open-label, early-access protocol trial in 23 countries. We enrolled patients who had metastatic castration-resistant prostate cancer progressing after taxane chemotherapy. Participants received oral doses of abiraterone acetate (1000 mg daily) and prednisone (5 mg twice a day) in 28-day cycles until disease progression, development of sustained side-effects, or abiraterone acetate becoming available in the respective country. The primary outcome was the number of adverse events arising during study treatment and within 30 days of discontinuation. Efficacy measures (time to prostate-specific antigen [PSA] progression and time to clinical progression) were gathered to guide treatment decisions. We included in our analysis all patients who received at least one dose of abiraterone acetate. This study is registered with ClinicalTrials.gov, number NCT01217697. Findings: Between Nov 17, 2010, and Sept 30, 2013, 2314 patients were enrolled into the early-access protocol trial. Median follow-up was 5·7 months (IQR 3·5-10·6). 952 (41%) patients had a grade 3 or 4 treatment-related adverse event, and grade 3 or 4 serious adverse events were recorded in 585 (25%) people. The most common grade 3 and 4 adverse events were hepatotoxicity (188 [8%]), hypertension (99 [4%]), cardiac disorders (52 [2%]), osteoporosis (31 [1%]), hypokalaemia (28 [1%]), and fluid retention or oedema (23 [1%]). 172 (7%) patients discontinued the study because of adverse events (64 [3%] were drug-related), as assessed by the investigator, and 171 (7%) people died. The funder assessed causes of death, which were due to disease progression (85 [4%]), an unrelated adverse experience (72 [3%]), and unknown reasons (14 [1%]). Of the 86 deaths not attributable to disease progression, 18 (<1%) were caused by a drug-related adverse event, as assessed by the investigator. Median time to PSA progression was 8·5 months (95% CI 8·3-9·7) and median time to clinical progression was 12·7 months (11·8-13·8). Interpretation: No new safety signals or unexpected adverse events were found in this early-access protocol trial to assess abiraterone acetate for patients with metastatic castration-resistant prostate cancer who progressed after chemotherapy. Future work is needed to ascertain the most effective regimen of abiraterone acetate to optimise patients' outcomes. Funding: Janssen Research & Development.
AB - Background: In the final analysis of the phase 3 COU-AA-301 study, abiraterone acetate plus prednisone significantly prolonged overall survival compared with prednisone alone in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. Here, we present the final analysis of an early-access protocol trial that was initiated after completion of COU-AA-301 to enable worldwide preapproval access to abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. Methods: We did a multicentre, open-label, early-access protocol trial in 23 countries. We enrolled patients who had metastatic castration-resistant prostate cancer progressing after taxane chemotherapy. Participants received oral doses of abiraterone acetate (1000 mg daily) and prednisone (5 mg twice a day) in 28-day cycles until disease progression, development of sustained side-effects, or abiraterone acetate becoming available in the respective country. The primary outcome was the number of adverse events arising during study treatment and within 30 days of discontinuation. Efficacy measures (time to prostate-specific antigen [PSA] progression and time to clinical progression) were gathered to guide treatment decisions. We included in our analysis all patients who received at least one dose of abiraterone acetate. This study is registered with ClinicalTrials.gov, number NCT01217697. Findings: Between Nov 17, 2010, and Sept 30, 2013, 2314 patients were enrolled into the early-access protocol trial. Median follow-up was 5·7 months (IQR 3·5-10·6). 952 (41%) patients had a grade 3 or 4 treatment-related adverse event, and grade 3 or 4 serious adverse events were recorded in 585 (25%) people. The most common grade 3 and 4 adverse events were hepatotoxicity (188 [8%]), hypertension (99 [4%]), cardiac disorders (52 [2%]), osteoporosis (31 [1%]), hypokalaemia (28 [1%]), and fluid retention or oedema (23 [1%]). 172 (7%) patients discontinued the study because of adverse events (64 [3%] were drug-related), as assessed by the investigator, and 171 (7%) people died. The funder assessed causes of death, which were due to disease progression (85 [4%]), an unrelated adverse experience (72 [3%]), and unknown reasons (14 [1%]). Of the 86 deaths not attributable to disease progression, 18 (<1%) were caused by a drug-related adverse event, as assessed by the investigator. Median time to PSA progression was 8·5 months (95% CI 8·3-9·7) and median time to clinical progression was 12·7 months (11·8-13·8). Interpretation: No new safety signals or unexpected adverse events were found in this early-access protocol trial to assess abiraterone acetate for patients with metastatic castration-resistant prostate cancer who progressed after chemotherapy. Future work is needed to ascertain the most effective regimen of abiraterone acetate to optimise patients' outcomes. Funding: Janssen Research & Development.
KW - Administration, Oral
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Androgen Antagonists
KW - Androstenols
KW - Disease Progression
KW - Disease-Free Survival
KW - Dose-Response Relationship, Drug
KW - Drug Administration Schedule
KW - Drug Therapy, Combination
KW - Humans
KW - Kaplan-Meier Estimate
KW - Male
KW - Middle Aged
KW - Neoplasm Invasiveness
KW - Neoplasm Recurrence, Local
KW - Neoplasm Staging
KW - Prednisolone
KW - Prognosis
KW - Prostate-Specific Antigen
KW - Prostatic Neoplasms, Castration-Resistant
KW - Survival Analysis
KW - Treatment Outcome
U2 - 10.1016/s1470-2045(14)70417-6
DO - 10.1016/s1470-2045(14)70417-6
M3 - Journal article
C2 - 25242048
SN - 1470-2045
VL - 15
SP - 1263
EP - 1268
JO - Lancet Oncology
JF - Lancet Oncology
IS - 11
ER -
