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. 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.

Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial / S. Horwitz, O.A. O'Connor, B. Pro, T. Illidge, M. Fanale, R. Advani, N.L. Bartlett, J.H. Christensen, F. Morschhauser, E. Domingo-Domenech, G. Rossi, W.S. Kim, T. Feldman, A. Lennard, D. Belada, Á. Illés, K. Tobinai, K. Tsukasaki, S. Yeh, A. Shustov, A. Hüttmann, K.J. Savage, S. Yuen, S. Iyer, P.L. Zinzani, Z. Hua, M. Little, S. Rao, J. Woolery, T. Manley, L. Trümper, D. Aboulafia, R. Advani, O. Alpdogan, K. Ando, L. Arcaini, L. Baldini, N. Bellam, N. Bartlett, D. Belada, D.B. Yehuda, F. Benedetti, P. Borchman, D. Bordessoule, P. Brice, J. Briones, D. Caballero, A.M. Carella, H. Chang, J.W. Cheong, S. Cho, I. Choi, S. Choquet, A. Colita, A.G. Congui, F. D'Amore, N. Dang, K. Davison, S. de Guibert, P.D.N. Brown, V. Delwail, J. Demeter, F. di Raimondo, Y.R. Do, E. Domingo, M. Douvas, M. Dreyling, T. Ernst, M. Fanale, K. Fay, T. Feldman, S.F. Ferrero, I.W. Flinn, A. Forero-Torres, C. Fox, J. Friedberg, N. Fukuhara, J. Garcia-Marco, J.G. Cruz, J.G. Codina, R. Gressin, A. Grigg, R. Gurion, J.H. Christensen, C. Haioun, R. Hajek, M. Hanel, K. Hatake, R. Hensen, N. Horowitz, S. Horwitz, A. Huttmann, A. Illes, T. Illidge, K. Ishizawa, M. Islas-Ohlmayer, E. Jacobsen, M. Janakiram, W. Jurczak, M. Kaminski, K. Kato, W.S. Kim, I. Kirgner, S. Iyer, C. Kuo, M.C. Lazaroiu, K.L. Du, J. Lee, S. Legouill, A. Lennard, P. Larosee, I. Levi, B. Link, H. Maisonneuve, D. Maruyama, J. Mayer, J. Mccarty, P. Mckay, Y. Minami, H. Mocikova, E. Morra, F. Morschhauser, J. Munoz, H. Nagai, O. O'Connor, S. Opat, R. Pettengell, A. Pezzutto, M. Pfreundschuh, A. Pluta, P. Porcu, B. Pro, H. Quach, A. Rambaldi, W. Renwick, R. Reyes, A.R. Izquierdo, G. Rossi, J. Ruan, C. Rusconi, G. Salles, A. Santoro, J. Sarriera, K. Savage, H. Shibayama, A. Shustov, C. Suh, A. Sureda, M. Tanimoto, M. Taniwaki, H. Tilly, K. Tobinai, M. Trneny, L. Trumper, N. Tsukamoto, K. Tsukasaki, U. Vitolo, J. Walewski, E. Weidmann, M. Wilhelm, M. Witzens-Harig, A. Yacoub, K. Yamamoto, S. Yeh, S. Yoon, S. Yuen, H.J. Yun, J. Zain, P.L. Zinzani. - In: THE LANCET. - ISSN 0140-6736. - 393:10168(2019 Jan 19), pp. 229-240. [10.1016/S0140-6736(18)32984-2]

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

L. Baldini;A. Rambaldi;
2019-01-19

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. 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.
Settore MED/15 - Malattie del Sangue
3-dic-2018
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/609944
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