Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2)

a global, double-blind, randomised, phase 3 trial

ECHELON-2 Study Group

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)229-240
Number of pages12
JournalThe Lancet
Volume393
Issue number10168
DOIs
Publication statusPublished - Jan 19 2019

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Peripheral T-Cell Lymphoma
Drug Therapy
Vincristine
Prednisone
Doxorubicin
Cyclophosphamide
Disease-Free Survival
Placebos
Safety
Anaplastic Large-Cell Lymphoma
Febrile Neutropenia
National Cancer Institute (U.S.)
National Institutes of Health (U.S.)
Peripheral Nervous System Diseases
Random Allocation
cAC10-vcMMAE
Pathology
Survival
Incidence
Therapeutics

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

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

In: The Lancet, Vol. 393, No. 10168, 19.01.2019, p. 229-240.

Research output: Contribution to journalArticle

@article{4331b48a419d47f2849fab04110d3ad7,
title = "Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial",
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.",
author = "{ECHELON-2 Study Group} and Steven Horwitz and O'Connor, {Owen A.} and Barbara Pro and Tim Illidge and Michelle Fanale and Ranjana Advani and Bartlett, {Nancy L.} and Christensen, {Jacob Haaber} and Franck Morschhauser and Eva Domingo-Domenech and Giuseppe Rossi and Kim, {Won Seog} and Tatyana Feldman and Anne Lennard and David Belada and {\'A}rp{\'a}d Ill{\'e}s and Kensei Tobinai and Kunihiro Tsukasaki and Yeh, {Su Peng} and Andrei Shustov and Andreas H{\"u}ttmann and Savage, {Kerry J.} and Sam Yuen and Swaminathan Iyer and Zinzani, {Pier Luigi} and Zhaowei Hua and Meredith Little and Shangbang Rao and Joseph Woolery and Thomas Manley and Lorenz Tr{\"u}mper and David Aboulafia and Onder Alpdogan and Kiyoshi Ando and Luca Arcaini and Luca Baldini and Naresh Bellam and Nancy Bartlett and Yehuda, {Dina Ben} and Fabio Benedetti and Peter Borchman and Dominique Bordessoule and Pauline Brice and Javier Briones and Dolores Caballero and Carella, {Angelo Michele} and Hung Chang and Cheong, {June Weon} and Cho, {Seok Goo} and Koji Kato",
year = "2019",
month = "1",
day = "19",
doi = "10.1016/S0140-6736(18)32984-2",
language = "English",
volume = "393",
pages = "229--240",
journal = "The Lancet",
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TY - JOUR

T1 - Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2)

T2 - a global, double-blind, randomised, phase 3 trial

AU - ECHELON-2 Study Group

AU - Horwitz, Steven

AU - O'Connor, Owen A.

AU - Pro, Barbara

AU - Illidge, Tim

AU - Fanale, Michelle

AU - Advani, Ranjana

AU - Bartlett, Nancy L.

AU - Christensen, Jacob Haaber

AU - Morschhauser, Franck

AU - Domingo-Domenech, Eva

AU - Rossi, Giuseppe

AU - Kim, Won Seog

AU - Feldman, Tatyana

AU - Lennard, Anne

AU - Belada, David

AU - Illés, Árpád

AU - Tobinai, Kensei

AU - Tsukasaki, Kunihiro

AU - Yeh, Su Peng

AU - Shustov, Andrei

AU - Hüttmann, Andreas

AU - Savage, Kerry J.

AU - Yuen, Sam

AU - Iyer, Swaminathan

AU - Zinzani, Pier Luigi

AU - Hua, Zhaowei

AU - Little, Meredith

AU - Rao, Shangbang

AU - Woolery, Joseph

AU - Manley, Thomas

AU - Trümper, Lorenz

AU - Aboulafia, David

AU - Alpdogan, Onder

AU - Ando, Kiyoshi

AU - Arcaini, Luca

AU - Baldini, Luca

AU - Bellam, Naresh

AU - Bartlett, Nancy

AU - Yehuda, Dina Ben

AU - Benedetti, Fabio

AU - Borchman, Peter

AU - Bordessoule, Dominique

AU - Brice, Pauline

AU - Briones, Javier

AU - Caballero, Dolores

AU - Carella, Angelo Michele

AU - Chang, Hung

AU - Cheong, June Weon

AU - Cho, Seok Goo

AU - Kato, Koji

PY - 2019/1/19

Y1 - 2019/1/19

N2 - 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.

AB - 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.

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U2 - 10.1016/S0140-6736(18)32984-2

DO - 10.1016/S0140-6736(18)32984-2

M3 - Article

VL - 393

SP - 229

EP - 240

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 10168

ER -