Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial.
Adult
Aged
Antineoplastic Agents
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Brentuximab Vedotin
Cyclophosphamide
/ administration & dosage
Disease-Free Survival
Double-Blind Method
Doxorubicin
/ administration & dosage
Female
Humans
Immunoconjugates
/ administration & dosage
Immunologic Factors
/ administration & dosage
Intention to Treat Analysis
Lymphoma, Large-Cell, Anaplastic
/ drug therapy
Male
Middle Aged
Prednisone
/ administration & dosage
Vincristine
/ administration & dosage
Journal
Lancet (London, England)
ISSN: 1474-547X
Titre abrégé: Lancet
Pays: England
ID NLM: 2985213R
Informations de publication
Date de publication:
19 01 2019
19 01 2019
Historique:
received:
17
10
2018
revised:
31
10
2018
accepted:
08
11
2018
pubmed:
14
12
2018
medline:
8
2
2019
entrez:
8
12
2018
Statut:
ppublish
Résumé
Based on the encouraging activity and manageable safety profile observed in a phase 1 study, the ECHELON-2 trial was initiated to compare the efficacy and safety of brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for the treatment of CD30-positive peripheral T-cell lymphomas. ECHELON-2 is a double-blind, double-dummy, randomised, placebo-controlled, active-comparator phase 3 study. Eligible adults from 132 sites in 17 countries with previously untreated CD30-positive peripheral T-cell lymphomas (targeting 75% with systemic anaplastic large cell lymphoma) were randomly assigned 1:1 to receive either A+CHP or CHOP for six or eight 21-day cycles. Randomisation was stratified by histological subtype according to local pathology assessment and by international prognostic index score. All patients received cyclophosphamide 750 mg/m Between Jan 24, 2013, and Nov 7, 2016, 601 patients assessed for eligibility, of whom 452 patients were enrolled and 226 were randomly assigned to both the A+CHP group and the CHOP group. Median progression-free survival was 48·2 months (95% CI 35·2-not evaluable) in the A+CHP group and 20·8 months (12·7-47·6) in the CHOP group (hazard ratio 0·71 [95% CI 0·54-0·93], p=0·0110). Adverse events, including incidence and severity of febrile neutropenia (41 [18%] patients in the A+CHP group and 33 [15%] in the CHOP group) and peripheral neuropathy (117 [52%] in the A+CHP group and 124 [55%] in the CHOP group), were similar between groups. Fatal adverse events occurred in seven (3%) patients in the A+CHP group and nine (4%) in the CHOP group. Front-line treatment with A+CHP is superior to CHOP for patients with CD30-positive peripheral T-cell lymphomas as shown by a significant improvement in progression-free survival and overall survival with a manageable safety profile. Seattle Genetics Inc, Millennium Pharmaceuticals Inc, a wholly owned subsidiary of Takeda Pharmacuetical Company Limited, and National Institutes of Health National Cancer Institute Cancer Center.
Sections du résumé
BACKGROUND
Based on the encouraging activity and manageable safety profile observed in a phase 1 study, the ECHELON-2 trial was initiated to compare the efficacy and safety of brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for the treatment of CD30-positive peripheral T-cell lymphomas.
METHODS
ECHELON-2 is a double-blind, double-dummy, randomised, placebo-controlled, active-comparator phase 3 study. Eligible adults from 132 sites in 17 countries with previously untreated CD30-positive peripheral T-cell lymphomas (targeting 75% with systemic anaplastic large cell lymphoma) were randomly assigned 1:1 to receive either A+CHP or CHOP for six or eight 21-day cycles. Randomisation was stratified by histological subtype according to local pathology assessment and by international prognostic index score. All patients received cyclophosphamide 750 mg/m
FINDINGS
Between Jan 24, 2013, and Nov 7, 2016, 601 patients assessed for eligibility, of whom 452 patients were enrolled and 226 were randomly assigned to both the A+CHP group and the CHOP group. Median progression-free survival was 48·2 months (95% CI 35·2-not evaluable) in the A+CHP group and 20·8 months (12·7-47·6) in the CHOP group (hazard ratio 0·71 [95% CI 0·54-0·93], p=0·0110). Adverse events, including incidence and severity of febrile neutropenia (41 [18%] patients in the A+CHP group and 33 [15%] in the CHOP group) and peripheral neuropathy (117 [52%] in the A+CHP group and 124 [55%] in the CHOP group), were similar between groups. Fatal adverse events occurred in seven (3%) patients in the A+CHP group and nine (4%) in the CHOP group.
INTERPRETATION
Front-line treatment with A+CHP is superior to CHOP for patients with CD30-positive peripheral T-cell lymphomas as shown by a significant improvement in progression-free survival and overall survival with a manageable safety profile.
FUNDING
Seattle Genetics Inc, Millennium Pharmaceuticals Inc, a wholly owned subsidiary of Takeda Pharmacuetical Company Limited, and National Institutes of Health National Cancer Institute Cancer Center.
Identifiants
pubmed: 30522922
pii: S0140-6736(18)32984-2
doi: 10.1016/S0140-6736(18)32984-2
pmc: PMC6436818
mid: NIHMS1515984
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Immunoconjugates
0
Immunologic Factors
0
Vincristine
5J49Q6B70F
Brentuximab Vedotin
7XL5ISS668
Doxorubicin
80168379AG
Cyclophosphamide
8N3DW7272P
Prednisone
VB0R961HZT
Banques de données
ClinicalTrials.gov
['NCT01777152']
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
229-240Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Investigateurs
David Aboulafia
(D)
Ranjana Advani
(R)
Onder Alpdogan
(O)
Kiyoshi Ando
(K)
Luca Arcaini
(L)
Luca Baldini
(L)
Naresh Bellam
(N)
Nancy Bartlett
(N)
David Belada
(D)
Dina Ben Yehuda
(DB)
Fabio Benedetti
(F)
Peter Borchman
(P)
Dominique Bordessoule
(D)
Pauline Brice
(P)
Javier Briones
(J)
Dolores Caballero
(D)
Angelo Michele Carella
(AM)
Hung Chang
(H)
June Weon Cheong
(JW)
Seok-Goo Cho
(SG)
Ilseung Choi
(I)
Sylvain Choquet
(S)
Andrei Colita
(A)
Angela Giovanna Congui
(AG)
Francesco D'amore
(F)
Nam Dang
(N)
Kelly Davison
(K)
Sophie de Guibert
(S)
Peter de Nully Brown
(PN)
Vincent Delwail
(V)
Judit Demeter
(J)
Francesco di Raimondo
(F)
Young Rok Do
(YR)
Eva Domingo
(E)
Michael Douvas
(M)
Martin Dreyling
(M)
Thomas Ernst
(T)
Michelle Fanale
(M)
Keith Fay
(K)
Tatyana Feldman
(T)
Silvia Fernandez Ferrero
(SF)
Ian Winchester Flinn
(IW)
Andres Forero-Torres
(A)
Christopher Fox
(C)
Jonathan Friedberg
(J)
Noriko Fukuhara
(N)
Jose Garcia-Marco
(J)
Jorge Gayoso Cruz
(JG)
Jose Gomez Codina
(JG)
Remy Gressin
(R)
Andrew Grigg
(A)
Ronit Gurion
(R)
Jacob Haaber Christensen
(JH)
Corinne Haioun
(C)
Roman Hajek
(R)
Mathias Hanel
(M)
Kiyohiko Hatake
(K)
Robert Hensen
(R)
Netanel Horowitz
(N)
Steven Horwitz
(S)
Andreas Huttmann
(A)
Arpad Illes
(A)
Tim Illidge
(T)
Kenichi Ishizawa
(K)
Miguel Islas-Ohlmayer
(M)
Eric Jacobsen
(E)
Murali Janakiram
(M)
Wojciech Jurczak
(W)
Mark Kaminski
(M)
Koji Kato
(K)
Won Seog Kim
(WS)
Ilya Kirgner
(I)
Swaminathan Iyer
(S)
Ching-Yuan Kuo
(CY)
Mihaela Cornelia Lazaroiu
(MC)
Katell Le Du
(KL)
Jong-Seok Lee
(JS)
Steven LeGouill
(S)
Anne Lennard
(A)
Paul LaRosee
(P)
Itai Levi
(I)
Brian Link
(B)
Herve Maisonneuve
(H)
Dai Maruyama
(D)
Jiri Mayer
(J)
John McCarty
(J)
Pam McKay
(P)
Yosuke Minami
(Y)
Heidi Mocikova
(H)
Enrica Morra
(E)
Franck Morschhauser
(F)
Javier Munoz
(J)
Hirokazu Nagai
(H)
Owen O'Connor
(O)
Stephen Opat
(S)
Ruth Pettengell
(R)
Antonio Pezzutto
(A)
Michael Pfreundschuh
(M)
Andrzej Pluta
(A)
PierLuigi Porcu
(P)
Barbara Pro
(B)
Hang Quach
(H)
Alessandro Rambaldi
(A)
William Renwick
(W)
Ruben Reyes
(R)
Antonia Rodriguez Izquierdo
(AR)
Giuseppe Rossi
(G)
Jia Ruan
(J)
Chiara Rusconi
(C)
Gilles Salles
(G)
Armando Santoro
(A)
Jose Sarriera
(J)
Kerry Savage
(K)
Hirohiko Shibayama
(H)
Andrei Shustov
(A)
Cheolwon Suh
(C)
Anna Sureda
(A)
Mitsune Tanimoto
(M)
Masafumi Taniwaki
(M)
Herve Tilly
(H)
Kensei Tobinai
(K)
Marek Trneny
(M)
Lorenz Trumper
(L)
Norifumi Tsukamoto
(N)
Kunihiro Tsukasaki
(K)
Umberto Vitolo
(U)
Jan Walewski
(J)
Eckhart Weidmann
(E)
Martin Wilhelm
(M)
Mathias Witzens-Harig
(M)
Abdulraheem Yacoub
(A)
Kazuhito Yamamoto
(K)
Su-Peng Yeh
(SP)
Sung-Soo Yoon
(SS)
Sam Yuen
(S)
Hwan Jung Yun
(HJ)
Jasmine Zain
(J)
Pier Luigi Zinzani
(PL)
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
Références
Ann Oncol. 2004 Oct;15(10):1467-75
pubmed: 15367405
J Clin Oncol. 2007 Feb 10;25(5):579-86
pubmed: 17242396
Blood. 2008 Jun 15;111(12):5496-504
pubmed: 18385450
J Clin Oncol. 2008 Sep 1;26(25):4124-30
pubmed: 18626005
J Clin Oncol. 2009 Jan 1;27(1):106-13
pubmed: 19029417
Blood. 2010 Nov 4;116(18):3418-25
pubmed: 20660290
Br J Haematol. 2010 Oct;151(2):159-66
pubmed: 20738307
Ann Oncol. 2011 Jul;22(7):1595-600
pubmed: 21212158
Adv Hematol. 2010;2010:624040
pubmed: 21234357
Blood. 2011 Mar 24;117(12):3402-8
pubmed: 21270441
Cancer. 2013 Jan 15;119(2):371-9
pubmed: 22833464
J Clin Oncol. 2012 Sep 1;30(25):3093-9
pubmed: 22851556
Leuk Lymphoma. 2013 Jul;54(7):1373-9
pubmed: 23278639
Blood. 2013 Mar 28;121(13):2529-32
pubmed: 23361910
Haematologica. 2013 Aug;98(8):e81-2
pubmed: 23716537
Semin Hematol. 2014 Jan;51(1):59-66
pubmed: 24468317
Blood. 2014 May 15;123(20):3095-100
pubmed: 24652992
Blood. 2014 Sep 4;124(10):1570-7
pubmed: 25006130
Blood. 2014 Nov 6;124(19):2983-6
pubmed: 25224410
Ann Oncol. 2015 Sep;26 Suppl 5:v108-15
pubmed: 26314772
Br J Haematol. 2016 Feb;172(4):535-44
pubmed: 26627450
Lancet Haematol. 2015 Apr;2(4):e160-5
pubmed: 26687958
J Natl Compr Canc Netw. 2016 Sep;14(9):1067-79
pubmed: 27587620
Cancer. 2017 Apr 1;123(7):1174-1183
pubmed: 27911989
Blood. 2017 Dec 21;130(25):2709-2717
pubmed: 28974506
Blood. 2018 May 10;131(19):2120-2124
pubmed: 29507077
Br J Haematol. 2018 Jun;181(6):760-769
pubmed: 29672827
Lancet Haematol. 2018 May;5(5):e190-e200
pubmed: 29703335
Control Clin Trials. 1996 Aug;17(4):343-6
pubmed: 8889347