Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer

Karim Fizazi, Nam Phuong Tran, Luis Fein, Nobuaki Matsubara, Alfredo Rodriguez-Antolin, Boris Y. Alekseev, Mustafa Özgüroglu, Dingwei Ye, Susan Feyerabend, Andrew Protheroe, Peter De Porre, Thian Kheoh, Youn C. Park, Mary B. Todd, Kim N. Chi, Umberto Basso

Research output: Contribution to journalArticle

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 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.).

Original languageEnglish
Pages (from-to)352-360
Number of pages9
JournalNew England Journal of Medicine
Volume377
Issue number4
DOIs
Publication statusPublished - Jul 27 2017

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Castration
Prednisone
Prostatic Neoplasms
Androgens
Placebos
Disease-Free Survival
Survival
Clinical Trials Data Monitoring Committees
Confidence Intervals
Therapeutics
Hypokalemia
Prostate-Specific Antigen
Tablets
Disease Progression
abiraterone
Hypertension
Safety
Drug Therapy
Pain
Abiraterone Acetate

ASJC Scopus subject areas

  • Medicine(all)

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Fizazi, K., Tran, N. P., Fein, L., Matsubara, N., Rodriguez-Antolin, A., Alekseev, B. Y., ... Basso, U. (2017). Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. New England Journal of Medicine, 377(4), 352-360. https://doi.org/10.1056/NEJMoa1704174

Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. / Fizazi, Karim; Tran, Nam Phuong; Fein, Luis; Matsubara, Nobuaki; Rodriguez-Antolin, Alfredo; Alekseev, Boris Y.; Özgüroglu, Mustafa; Ye, Dingwei; Feyerabend, Susan; Protheroe, Andrew; De Porre, Peter; Kheoh, Thian; Park, Youn C.; Todd, Mary B.; Chi, Kim N.; Basso, Umberto.

In: New England Journal of Medicine, Vol. 377, No. 4, 27.07.2017, p. 352-360.

Research output: Contribution to journalArticle

Fizazi, K, Tran, NP, Fein, L, Matsubara, N, Rodriguez-Antolin, A, Alekseev, BY, Özgüroglu, M, Ye, D, Feyerabend, S, Protheroe, A, De Porre, P, Kheoh, T, Park, YC, Todd, MB, Chi, KN & Basso, U 2017, 'Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer', New England Journal of Medicine, vol. 377, no. 4, pp. 352-360. https://doi.org/10.1056/NEJMoa1704174
Fizazi K, Tran NP, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. New England Journal of Medicine. 2017 Jul 27;377(4):352-360. https://doi.org/10.1056/NEJMoa1704174
Fizazi, Karim ; Tran, Nam Phuong ; Fein, Luis ; Matsubara, Nobuaki ; Rodriguez-Antolin, Alfredo ; Alekseev, Boris Y. ; Özgüroglu, Mustafa ; Ye, Dingwei ; Feyerabend, Susan ; Protheroe, Andrew ; De Porre, Peter ; Kheoh, Thian ; Park, Youn C. ; Todd, Mary B. ; Chi, Kim N. ; Basso, Umberto. / Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. In: New England Journal of Medicine. 2017 ; Vol. 377, No. 4. pp. 352-360.
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T1 - Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer

AU - Fizazi, Karim

AU - Tran, Nam Phuong

AU - Fein, Luis

AU - Matsubara, Nobuaki

AU - Rodriguez-Antolin, Alfredo

AU - Alekseev, Boris Y.

AU - Özgüroglu, Mustafa

AU - Ye, Dingwei

AU - Feyerabend, Susan

AU - Protheroe, Andrew

AU - De Porre, Peter

AU - Kheoh, Thian

AU - Park, Youn C.

AU - Todd, Mary B.

AU - Chi, Kim N.

AU - Basso, Umberto

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N2 - 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.).

AB - 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.).

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