• Steven Horwitz, Owen A O'Connor, Barbara Pro, Tim Illidge, Michelle Fanale, Ranjana Advani, Nancy L Bartlett, Jacob Haaber Christensen, Franck Morschhauser, Eva Domingo-Domenech, Giuseppe Rossi, Won Seog Kim, Tatyana Feldman, Anne Lennard, David Belada, Árpád Illés, Kensei Tobinai, Kunihiro Tsukasaki, Su-Peng Yeh, Andrei Shustov, Andreas Hüttmann, Kerry J Savage, Sam Yuen, Swaminathan Iyer, Pier Luigi Zinzani, Zhaowei Hua, Meredith Little, Shangbang Rao, Joseph Woolery, Thomas Manley, Lorenz Trümper, and ECHELON-2 Study Group.
• Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: horwitzs@mskcc.org.
• Lancet. 2019 Jan 19; 393 (10168): 229-240.

BackgroundBased 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.MethodsECHELON-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.FindingsBetween 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.InterpretationFront-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.FundingSeattle Genetics Inc, Millennium Pharmaceuticals Inc, a wholly owned subsidiary of Takeda Pharmacuetical Company Limited, and National Institutes of Health National Cancer Institute Cancer Center.Copyright © 2019 Elsevier Ltd. All rights reserved.

30 keywords...

hide…