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Lancet. 2019 Jan 19;393(10168):229-240. doi: 10.1016/S0140-6736(18)32984-2. Epub 2018 Dec 4.

Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial.

Collaborators (138)

Aboulafia D, Advani R, Alpdogan O, Ando K, Arcaini L, Baldini L, Bellam N, Bartlett N, Belada D, Yehuda DB, Benedetti F, Borchman P, Bordessoule D, Brice P, Briones J, Caballero D, Carella AM, Chang H, Cheong JW, Cho SG, Choi I, Choquet S, Colita A, Congui AG, D'amore F, Dang N, Davison K, de Guibert S, Brown PN, Delwail V, Demeter J, di Raimondo F, Do YR, Domingo E, Douvas M, Dreyling M, Ernst T, Fanale M, Fay K, Feldman T, Ferrero SF, Flinn IW, Forero-Torres A, Fox C, Friedberg J, Fukuhara N, Garcia-Marco J, Cruz JG, Codina JG, Gressin R, Grigg A, Gurion R, Christensen JH, Haioun C, Hajek R, Hanel M, Hatake K, Hensen R, Horowitz N, Horwitz S, Huttmann A, Illes A, Illidge T, Ishizawa K, Islas-Ohlmayer M, Jacobsen E, Janakiram M, Jurczak W, Kaminski M, Kato K, Kim WS, Kirgner I, Iyer S, Kuo CY, Lazaroiu MC, Du KL, Lee JS, LeGouill S, Lennard A, LaRosee P, Levi I, Link B, Maisonneuve H, Maruyama D, Mayer J, McCarty J, McKay P, Minami Y, Mocikova H, Morra E, Morschhauser F, Munoz J, Nagai H, O'Connor O, Opat S, Pettengell R, Pezzutto A, Pfreundschuh M, Pluta A, Porcu P, Pro B, Quach H, Rambaldi A, Renwick W, Reyes R, Izquierdo AR, Rossi G, Ruan J, Rusconi C, Salles G, Santoro A, Sarriera J, Savage K, Shibayama H, Shustov A, Suh C, Sureda A, Tanimoto M, Taniwaki M, Tilly H, Tobinai K, Trneny M, Trumper L, Tsukamoto N, Tsukasaki K, Vitolo U, Walewski J, Weidmann E, Wilhelm M, Witzens-Harig M, Yacoub A, Yamamoto K, Yeh SP, Yoon SS, Yuen S, Yun HJ, Zain J, Zinzani PL.

Author information

1
Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: horwitzs@mskcc.org.
2
Columbia University Medical Center, New York, NY, USA.
3
Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
4
Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, National Institutes of Health and Research Biomedical Research Centre, Manchester Academic Health Sciences Centre, Christie Hospital National Health Service Foundation Trust, Manchester, UK.
5
MD Anderson Cancer Center, University of Texas, Houston, TX, USA; Seattle Genetics, Inc, Bothell, WA, USA.
6
Stanford Cancer Center, Blood and Marrow Transplant Program, Stanford, CA, USA.
7
Washington University School of Medicine, St Louis, MI, USA.
8
Odense University Hospital, Odense, Denmark.
9
University of Lille, Centre Hospitalier Universitaire de Lille, Groupe de Recherche sur les formes Injectables et les Technologies Associées, Lille, France.
10
Institut Catala D'oncologia, L'Hospitalet de Llobregat, Barcelona, Spain.
11
Azienda Ospedaliera Spedali Civili di Brescia, Brescia, Italy.
12
Samsung Medical Center, Seoul, South Korea.
13
Hackensack University Medical Center, Hackensack, NJ, USA.
14
Freeman Hospital, Newcastle upon Tyne, UK.
15
4th Department of Internal Medicine-Haematology, Charles University, Hospital and Faculty of Medicine, Hradec Králové, Czech Republic.
16
University of Debrecen, Faculty of Medicine, Department of Hematology, Debrecen, Hungary.
17
National Cancer Center Hospital, Tokyo, Japan.
18
Saitama Medical University International Medical Center, Saitama, Japan.
19
China Medical University Hospital, Taichung, Taiwan.
20
University of Washington Medical Center, Seattle, WA, USA.
21
Universitatsklinikum Essen, Essen, Nordrhein-Westfalen, Germany.
22
University of British Columbia and the Department of Medical Oncology, British Columbia Cancer Centre for Lymphoid Cancer, Vancouver, BC, Canada.
23
Calvary Mater Newcastle Hospital, Waratah, NSW, Australia.
24
MD Anderson Cancer Center, University of Texas, Houston, TX, USA.
25
Institute of Hematology Seràgnoli, University of Bologna, Bologna, Italy.
26
Millennium Pharmaceuticals, Inc, Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company.
27
Seattle Genetics, Inc, Bothell, WA, USA.
28
Universitätsmedizin Göttingen, Göttingen, Germany.

Erratum in

Abstract

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/m2 and doxorubicin 50 mg/m2 on day 1 of each cycle intravenously and prednisone 100 mg once daily on days 1 to 5 of each cycle orally, followed by either brentuximab vedotin 1·8 mg/kg and a placebo form of vincristine intravenously (A+CHP group) or vincristine 1·4 mg/m2 and a placebo form of brentuximab vedotin intravenously (CHOP group) on day 1 of each cycle. The primary endpoint, progression-free survival according to blinded independent central review, was analysed by intent-to-treat. This trial is registered with ClinicalTrials.gov, number NCT01777152.

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.

PMID:
30522922
PMCID:
PMC6436818
[Available on 2020-01-19]
DOI:
10.1016/S0140-6736(18)32984-2
[Indexed for MEDLINE]

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