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

Item Type:	Article
Title:	Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial
Creators Name:	Horwitz, S. and O'Connor, O.A. and Pro, B. and Illidge, T. and Fanale, M. and Advani, R. and Bartlett, N.L. and Christensen, J.H. and Morschhauser, F. and Domingo-Domenech, E. and Rossi, G. and Kim, W.S. and Feldman, T. and Lennard, A. and Belada, D. and Illés, A. and Tobinai, K. and Tsukasaki, K. and Yeh, S.P. and Shustov, A. and Hüttmann, A. and Savage, K.J. and Yuen, S. and Iyer, S. and Zinzani, P.L. and Hua, Z. and Little, M. and Rao, S. and Woolery, J. and Manley, T. and Trümper, L.
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/m(2) and doxorubicin 50 mg/m(2) 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/m(2) 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.
Keywords:	Anaplastic Large-Cell Lymphoma, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Brentuximab Vedotin, Cyclophosphamide, Disease-Free Survival, Double-Blind Method, Doxorubicin, Immunoconjugates, Immunologic Factors, Intention to Treat Analysis, Prednisone, Vincristine
Source:	Lancet
ISSN:	0140-6736
Publisher:	Elsevier
Volume:	393
Number:	10168
Page Range:	229-240
Date:	19 January 2019
Additional Information:	Antonio Pezzutto is an ECHELON-2 investigator.
Official Publication:	https://doi.org/10.1016/S0140-6736(18)32984-2
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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