Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer
(2017) In New England Journal of Medicine 377(4). p.352-360- Abstract
BACKGROUND: Abiraterone acetate, a drug that blocks endogenous androgen synthesis, plus prednisone is indicated for metastatic castration-resistant prostate cancer. We evaluated the clinical benefit of abiraterone acetate plus prednisone with androgen-deprivation therapy in patients with newly diagnosed, metastatic, castration-sensitive prostate cancer.
METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 1199 patients to receive either androgen-deprivation therapy plus abiraterone acetate (1000 mg daily, given once daily as four 250-mg tablets) plus prednisone (5 mg daily) (the abiraterone group) or androgen-deprivation therapy plus dual placebos (the placebo group). The two primary end points... (More)
BACKGROUND: Abiraterone acetate, a drug that blocks endogenous androgen synthesis, plus prednisone is indicated for metastatic castration-resistant prostate cancer. We evaluated the clinical benefit of abiraterone acetate plus prednisone with androgen-deprivation therapy in patients with newly diagnosed, metastatic, castration-sensitive prostate cancer.
METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 1199 patients to receive either androgen-deprivation therapy plus abiraterone acetate (1000 mg daily, given once daily as four 250-mg tablets) plus prednisone (5 mg daily) (the abiraterone group) or androgen-deprivation therapy plus dual placebos (the placebo group). The two primary end points were overall survival and radiographic progression-free survival.
RESULTS: After a median follow-up of 30.4 months at a planned interim analysis (after 406 patients had died), the median overall survival was significantly longer in the abiraterone group than in the placebo group (not reached vs. 34.7 months) (hazard ratio for death, 0.62; 95% confidence interval [CI], 0.51 to 0.76; P<0.001). The median length of radiographic progression-free survival was 33.0 months in the abiraterone group and 14.8 months in the placebo group (hazard ratio for disease progression or death, 0.47; 95% CI, 0.39 to 0.55; P<0.001). Significantly better outcomes in all secondary end points were observed in the abiraterone group, including the time until pain progression, next subsequent therapy for prostate cancer, initiation of chemotherapy, and prostate-specific antigen progression (P<0.001 for all comparisons), along with next symptomatic skeletal events (P=0.009). These findings led to the unanimous recommendation by the independent data and safety monitoring committee that the trial be unblinded and crossover be allowed for patients in the placebo group to receive abiraterone. Rates of grade 3 hypertension and hypokalemia were higher in the abiraterone group.
CONCLUSIONS: The addition of abiraterone acetate and prednisone to androgen-deprivation therapy significantly increased overall survival and radiographic progression-free survival in men with newly diagnosed, metastatic, castration-sensitive prostate cancer. (Funded by Janssen Research and Development; LATITUDE ClinicalTrials.gov number, NCT01715285 .).
(Less)
- author
- contributor
- Bjartell, Anders LU
- author collaboration
- organization
- publishing date
- 2017-07-27
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Abiraterone Acetate/administration & dosage, Adult, Aged, Aged, 80 and over, Androgen Antagonists/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Humans, Male, Middle Aged, Neoplasm Metastasis/drug therapy, Prednisolone/administration & dosage, Prostatic Neoplasms/drug therapy, Steroid 17-alpha-Hydroxylase/antagonists & inhibitors, Survival Analysis
- in
- New England Journal of Medicine
- volume
- 377
- issue
- 4
- pages
- 9 pages
- publisher
- Massachusetts Medical Society
- external identifiers
-
- pmid:28578607
- scopus:85020848493
- ISSN
- 0028-4793
- DOI
- 10.1056/NEJMoa1704174
- language
- English
- LU publication?
- yes
- id
- 42f9871f-59de-46e8-bc83-4c35a3022ae1
- date added to LUP
- 2019-06-26 10:38:39
- date last changed
- 2024-04-16 12:52:00
@article{42f9871f-59de-46e8-bc83-4c35a3022ae1,
abstract = {{<p>BACKGROUND: Abiraterone acetate, a drug that blocks endogenous androgen synthesis, plus prednisone is indicated for metastatic castration-resistant prostate cancer. We evaluated the clinical benefit of abiraterone acetate plus prednisone with androgen-deprivation therapy in patients with newly diagnosed, metastatic, castration-sensitive prostate cancer.</p><p>METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 1199 patients to receive either androgen-deprivation therapy plus abiraterone acetate (1000 mg daily, given once daily as four 250-mg tablets) plus prednisone (5 mg daily) (the abiraterone group) or androgen-deprivation therapy plus dual placebos (the placebo group). The two primary end points were overall survival and radiographic progression-free survival.</p><p>RESULTS: After a median follow-up of 30.4 months at a planned interim analysis (after 406 patients had died), the median overall survival was significantly longer in the abiraterone group than in the placebo group (not reached vs. 34.7 months) (hazard ratio for death, 0.62; 95% confidence interval [CI], 0.51 to 0.76; P<0.001). The median length of radiographic progression-free survival was 33.0 months in the abiraterone group and 14.8 months in the placebo group (hazard ratio for disease progression or death, 0.47; 95% CI, 0.39 to 0.55; P<0.001). Significantly better outcomes in all secondary end points were observed in the abiraterone group, including the time until pain progression, next subsequent therapy for prostate cancer, initiation of chemotherapy, and prostate-specific antigen progression (P<0.001 for all comparisons), along with next symptomatic skeletal events (P=0.009). These findings led to the unanimous recommendation by the independent data and safety monitoring committee that the trial be unblinded and crossover be allowed for patients in the placebo group to receive abiraterone. Rates of grade 3 hypertension and hypokalemia were higher in the abiraterone group.</p><p>CONCLUSIONS: The addition of abiraterone acetate and prednisone to androgen-deprivation therapy significantly increased overall survival and radiographic progression-free survival in men with newly diagnosed, metastatic, castration-sensitive prostate cancer. (Funded by Janssen Research and Development; LATITUDE ClinicalTrials.gov number, NCT01715285 .).</p>}},
author = {{Fizazi, Karim and Tran, NamPhuong and Fein, Luis and Matsubara, Nobuaki and Rodriguez-Antolin, Alfredo and Alekseev, Boris Y and Özgüroğlu, Mustafa and Ye, Dingwei and Feyerabend, Susan and Protheroe, Andrew and De Porre, Peter and Kheoh, Thian and Park, Youn C and Todd, Mary B and Chi, Kim N}},
issn = {{0028-4793}},
keywords = {{Abiraterone Acetate/administration & dosage; Adult; Aged; Aged, 80 and over; Androgen Antagonists/administration & dosage; Antineoplastic Combined Chemotherapy Protocols/adverse effects; Humans; Male; Middle Aged; Neoplasm Metastasis/drug therapy; Prednisolone/administration & dosage; Prostatic Neoplasms/drug therapy; Steroid 17-alpha-Hydroxylase/antagonists & inhibitors; Survival Analysis}},
language = {{eng}},
month = {{07}},
number = {{4}},
pages = {{352--360}},
publisher = {{Massachusetts Medical Society}},
series = {{New England Journal of Medicine}},
title = {{Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer}},
url = {{http://dx.doi.org/10.1056/NEJMoa1704174}},
doi = {{10.1056/NEJMoa1704174}},
volume = {{377}},
year = {{2017}},
}