Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer.

Adenocarcinoma / drug therapy Adult Aged Aged, 80 and over Androgen Antagonists / adverse effects Androgen Receptor Antagonists / adverse effects Antineoplastic Combined Chemotherapy Protocols / therapeutic use Double-Blind Method Exanthema / chemically induced Humans Kaplan-Meier Estimate Male Middle Aged Neoplasm Grading Progression-Free Survival Prostatic Neoplasms / drug therapy Quality of Life Radiography Thiohydantoins / adverse effects

Journal

The New England journal of medicine

ISSN: 1533-4406

Titre abrégé: N Engl J Med

Pays: United States

ID NLM: 0255562

Informations de publication

Date de publication:
04 07 2019

Historique:

pubmed: 1 6 2019

medline: 30 7 2019

entrez: 1 6 2019

Statut: ppublish

Résumé

Apalutamide is an inhibitor of the ligand-binding domain of the androgen receptor. Whether the addition of apalutamide to androgen-deprivation therapy (ADT) would prolong radiographic progression-free survival and overall survival as compared with placebo plus ADT among patients with metastatic, castration-sensitive prostate cancer has not been determined. In this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castration-sensitive prostate cancer to receive apalutamide (240 mg per day) or placebo, added to ADT. Previous treatment for localized disease and previous docetaxel therapy were allowed. The primary end points were radiographic progression-free survival and overall survival. A total of 525 patients were assigned to receive apalutamide plus ADT and 527 to receive placebo plus ADT. The median age was 68 years. A total of 16.4% of the patients had undergone prostatectomy or received radiotherapy for localized disease, and 10.7% had received previous docetaxel therapy; 62.7% had high-volume disease, and 37.3% had low-volume disease. At the first interim analysis, with a median of 22.7 months of follow-up, the percentage of patients with radiographic progression-free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (hazard ratio for radiographic progression or death, 0.48; 95% confidence interval [CI], 0.39 to 0.60; P<0.001). Overall survival at 24 months was also greater with apalutamide than with placebo (82.4% in the apalutamide group vs. 73.5% in the placebo group; hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P = 0.005). The frequency of grade 3 or 4 adverse events was 42.2% in the apalutamide group and 40.8% in the placebo group; rash was more common in the apalutamide group. In this trial involving patients with metastatic, castration-sensitive prostate cancer, overall survival and radiographic progression-free survival were significantly longer with the addition of apalutamide to ADT than with placebo plus ADT, and the side-effect profile did not differ substantially between the two groups. (Funded by Janssen Research and Development; TITAN ClinicalTrials.gov number, NCT02489318.).

Sections du résumé

BACKGROUND

METHODS

In this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castration-sensitive prostate cancer to receive apalutamide (240 mg per day) or placebo, added to ADT. Previous treatment for localized disease and previous docetaxel therapy were allowed. The primary end points were radiographic progression-free survival and overall survival.

RESULTS

A total of 525 patients were assigned to receive apalutamide plus ADT and 527 to receive placebo plus ADT. The median age was 68 years. A total of 16.4% of the patients had undergone prostatectomy or received radiotherapy for localized disease, and 10.7% had received previous docetaxel therapy; 62.7% had high-volume disease, and 37.3% had low-volume disease. At the first interim analysis, with a median of 22.7 months of follow-up, the percentage of patients with radiographic progression-free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (hazard ratio for radiographic progression or death, 0.48; 95% confidence interval [CI], 0.39 to 0.60; P<0.001). Overall survival at 24 months was also greater with apalutamide than with placebo (82.4% in the apalutamide group vs. 73.5% in the placebo group; hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P = 0.005). The frequency of grade 3 or 4 adverse events was 42.2% in the apalutamide group and 40.8% in the placebo group; rash was more common in the apalutamide group.

CONCLUSIONS

In this trial involving patients with metastatic, castration-sensitive prostate cancer, overall survival and radiographic progression-free survival were significantly longer with the addition of apalutamide to ADT than with placebo plus ADT, and the side-effect profile did not differ substantially between the two groups. (Funded by Janssen Research and Development; TITAN ClinicalTrials.gov number, NCT02489318.).

Identifiants

DOI: 10.1056/NEJMoa1903307 PMID: 31150574

pubmed: 31150574

doi: 10.1056/NEJMoa1903307

doi:

Substances chimiques

Androgen Antagonists 0

Androgen Receptor Antagonists 0

Thiohydantoins 0

apalutamide 0

Banques de données

ClinicalTrials.gov

['NCT02489318']

Types de publication

Clinical Trial, Phase III Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Pagination

13-24

Investigateurs

Emilio Batagelj (E)

Sergio Bayo (S)

Santiago Bella (S)

Mario Luis De Romedi (ML)

Luis Fein (L)

Martin Alberto Greco (MA)

Susana Kahl (S)

Ernesto Korbenfeld (E)

Luis Fernando Montes de Oca (LF)

Martin Richardet (M)

Alejandro Salvatierra (A)

Esteban Staneloni (E)

Mirta Varela (M)

Juan Jose Zarba (JJ)

Stephen Begbie (S)

Christopher Hocking (C)

Laurence Krieger (L)

Christopher Steer (C)

Flávio Carcano (F)

Carlos José Coelho de Andrade (CJ)

Alexandre Crippa (A)

Felipe Cruz (F)

Ronaldo Damião (R)

Gilson Delgado (G)

Aldo Dettino (A)

Adilson Faccio (A)

Fabio Franke (F)

Marcelo Freitas (M)

Andrea Juliana Gomes (AJ)

Gisele Marinho (G)

Suelen Martins (S)

William Nahas (W)

Roberto Odebrecht (R)

Renato Panhoca (R)

Adriano Paula (A)

Oren Smaletz (O)

Brigitte van Eyll (B)

Kim Chi (K)

Neil Fleshner (N)

Yves Fradet (Y)

Bobby Shayegan (B)

Robert Siemens (R)

Geoffrey Gotto (G)

Zhiwen Chen (Z)

Chuanjun Du (C)

Hongqian Guo (H)

Dalin He (D)

Qiang Hu (Q)

Jian Huang (J)

Jie Jin (J)

Hong Luo (H)

Lulin Ma (L)

Jinxian Pu (J)

Mingxing Qiu (M)

Zhongquan Sun (Z)

Ye Tian (Y)

Ben Wan (B)

Shujie Xia (S)

Enci Xu (E)

Yong Yang (Y)

Dingwei Ye (D)

Zhangqun Ye (Z)

Qing Zou (Q)

Ivan Andel (I)

Milos Brodak (M)

Otakar Capoun (O)

Jan Dvorak (J)

Petra Holeckova (P)

Ladislav Jarolim (L)

Michaela Matouskova (M)

Jan Mecl (J)

Hana Perkova (H)

Roman Stanek (R)

Vladimir Student (V)

Jaroslav Vanasek (J)

Roman Zachoval (R)

Mostefa Bennamoun (M)

Laurent Guy (L)

Thierry Lebret (T)

Alain Ruffion (A)

Dominique Spaeth (D)

Youssef Tazi (Y)

Marc-Olivier Timsit (MO)

Ralf Eckert (R)

Susan Feyerabend (S)

Peter Hammerer (P)

Matthias May (M)

Axel Merseburger (A)

Henrik Suttmann (H)

Silvio Szymula (S)

Christoph von Klot (C)

Gyorgy Bodoky (G)

Lajos Géczi (L)

Dániel Kulcsár (D)

Péter Nyirády (P)

Ferenc Torzsok (F)

Tibor Trautmann (T)

Daniel Kejzman (D)

Wilmosh Mermershtain (W)

Avivit Peer (A)

Eli Rosenbaum (E)

Avishay Sella (A)

Claudia Caserta (C)

Luca Galli (L)

Afete Hamzaj (A)

Michele Milella (M)

Franco Morelli (F)

Alessandra Mosca (A)

Claudia Mucciarini (C)

Giuseppe Procopio (G)

Giorgio Scagliotti (G)

Alessandro Sciarra (A)

Gaku Arai (G)

Satoshi Fukasawa (S)

Katsuyoshi Hashine (K)

Kazuyoshi Iijima (K)

Ryuji Matsumoto (R)

Kazuo Nishimura (K)

Takeo Nomura (T)

Hideki Sakai (H)

Hiroyoshi Suzuki (H)

Hiromasa Tsukino (H)

Hideyasu Tsumura (H)

Hiroji Uemura (H)

Hirotsugu Uemura (H)

Akito Yamaguchi (A)

David Calvo (D)

Armando Castro (A)

Arturo Rodriguez (A)

Narciso Hernandez (N)

Roberto Kuri (R)

Ivan Martinez (I)

Emilio Murillo (E)

Lizbett Garcia (L)

Piotr Humanski (P)

Jacek Jarzemski (J)

Adam Marcheluk (A)

Elzbieta Oszukowska (E)

Iwona Skoneczna (I)

Marcin Zaremba (M)

Seoksoo Byun (S)

Byungha Chung (B)

Sung Joon Hong (SJ)

SungGu Kang (S)

Choung Soo Kim (CS)

Cheol Kwak (C)

DongDeuk Kwon (D)

TaeGyun Kwon (T)

Ji Youl Lee (JY)

Kanghyun Lee (K)

SeongIl Seo (S)

Ki Hak Song (KH)

Viorel Jinga (V)

Dan Lungulescu (D)

Claudia Militaru (C)

Boris Alekseev (B)

Nikolay Budnik (N)

Valery Chistyakov (V)

Rustem Gafanov (R)

Oleg Karyakin (O)

Denis Khvorostenko (D)

Gennady Kolesnikov (G)

Evgeny Kopyltsov (E)

Sergey Kovalskiy (S)

Eugeny Kulikov (E)

Adel Izmaylov (A)

Alexander Lykov (A)

Mark Mamonov (M)

Alexander Mangushlo (A)

Vsevolod Matveev (V)

Andrey Semenov (A)

Vasily Shirshov (V)

Mikhail Shkolnik (M)

Pavel Skopin (P)

Roman Smirnov (R)

Anton Tishchenko (A)

Sergey Varlamov (S)

Eugeny Veliev (E)

Vladimir Vladimirov (V)

Jesus Garcia Donas (J)

Alvaro Juarez (A)

Asier Leivar (A)

Carlos Llorente (C)

Ma José Requena (MJ)

Alfredo Rodríguez-Antolín (A)

Ove Andren (O)

Anders Bjartell (A)

Jan-Erik Damber (JE)

Amer Elwaheidy (A)

Michael Haggman (M)

Borje Ljungberg (B)

Ulf Norming (U)

Bulent Akdogan (B)

Cagatay Arslan (C)

Sumer Baltaci (S)

Cag Cal (C)

Irfan Cicin (I)

Mustafa Ozguroglu (M)

Sinan Sozen (S)

Emel Yaman Sezer (E)

Bulent Yalcin (B)

Orhan Yigitbasi (O)

Igor Bondarenko (I)

Iaroslav Gotsuliak (I)

Valeriy Hodos (V)

Eugene Hotko (E)

Petro Ivashchenko (P)

Gennadii Khareba (G)

Oleksandr Kostiuk (O)

Oleksandr Lychkovskyy (O)

Oleksiy Lyulko (O)

Viktor Paramonov (V)

Oleksiy Pidmurnyak (O)

Vadym Pryanikov (V)

Valerii Sakalo (V)

Ievgenii Sonnyk (I)

Eduard Stakhovsky (E)

Viktor Stus (V)

Jonathan Aning (J)

Simon Chowdhury (S)

Sanjay Dixit (S)

Rob Jones (R)

Anil Kumar (A)

Darren Leaning (D)

Ghulam Nabi (G)

Salvatore Natale (S)

Andrew Protheroe (A)

Ian Sayers (I)

Neeraj Agarwal (N)

Manish Agrawal (M)

Sunil Babu (S)

James Bailen (J)

Stephen Bardot (S)

Laurence Belkoff (L)

Kathryn Bylow (K)

Franklin Chu (F)

James Cochran (J)

Mark DeGuenther (M)

Gurjyot Doshi (G)

Curtis Dunshee (C)

Jeffrey Frankel (J)

Benjamin Gartrell (B)

Lawrence Gervasi (L)

Robert Given (R)

Michael Goodman (M)

Jason Hafron (J)

Ralph Hauke (R)

Mark Jalkut (M)

Lawrence Karsh (L)

Brian Lewis (B)

Heather Mannuel (H)

Bryan Mehlhaff (B)

David Morris (D)

Nicklas Pfanzelter (N)

Christopher Pieczonka (C)

Paul Sieber (P)

Daniel Saltzstein (D)

Zvi Schiffman (Z)

Roohollah Sharifi (R)

Ronald Tutrone (R)

Commentaires et corrections

Type : CommentIn