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

Tools

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., O'Connor, O.A., Pro, B., Illidge, T., Fanale, M., Advani, R., Bartlett, N.L., Christensen, J.H., Morschhauser, F., Domingo-Domenech, E., Rossi, G., Kim, W.S., Feldman, T., Lennard, A., Belada, D., Illés, A., Tobinai, K., Tsukasaki, K., Yeh, S.P., Shustov, A., Hüttmann, A., Savage, K.J., Yuen, S., Iyer, S., Zinzani, P.L., Hua, Z., Little, M., Rao, S., Woolery, J., 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

Repository Staff Only: item control page