Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 in comparison with rituximab in patients with previously untreated low-tumour-burden follicular lymphoma: a randomised, double-blind, parallel-group, phase 3 trial
Por:
Ogura, M, Sancho, JM, Cho, SG, Nakazawa, H, Suzumiya, J, Tumyan, G, Kim, JS, Lennard, A, Mariz, J, Ilyin, N, Jurczak, W, Martinez, AL, Samoilova, O, Zhavrid, E, Ruiz, EY, Trneny, M, Popplewell, L, Coiffier, B, Buske, C, Kim, WS, Lee, SJ, Lee, SY, Bae, YJ and Kwak, LW
Publicada:
1 nov 2018
Categoría:
Hematology
Resumen:
Background Studies in patients with rheumatoid arthritis and advanced follicular lymphoma have shown that CT-P10, a rituximab biosimilar, has equivalent or non-inferior efficacy and pharmacokinetics to rituximab. We aimed to assess the therapeutic equivalence of single-agent CT-P10 and rituximab in patients with newly diagnosed low-tumour burden follicular lytnpliorna.
Methods In this ongoing, randomised, double-blind, parallel-group, active-controlled, phase 3 trial, adult patients W.8 years) with stage II-IV low-tumour-burden follicular lymphoma were randomly assigned (1:1) using an interactive web or voice response system stratified by region, stage, and age to CT-P10 or US-sourced rituximab. Patients received CT-P10 or rituximab (375 mg/m(2) intravenous) on day 1 of four 7-day cycles (induction period). Patients who had disease control after the induction period continued to a maintenance period of CT-P10 or rituximab administered every 8 weeks for six cycles and, if completed, a second year of maintenance therapy of additional CT-P10 (every 8 weeks for six cycles) was offered. The study was partially unmasked after database lock (Feb 23, 2018) for all data up to 7 months (before cycle 3 of the maintenance period). The primary endpoint was the proportion of patients who achieved an overall response by 7 months in the intention-to-treat population. Efficacy equivalence was shown if the two-sided 90% CIs for the treatment difference in the proportion of responders between CT-P10 and rituximab was within the equivalence margin of 17%. This trial is registered with ClinicalTrials.gov, number NCT02260804.
Findings Between Nov 9, 2015, and Jan 4, 2018, 402 patients were assessed for eligibility, of whom 258 were randomly assigned: 130 to CT-P10 and 128 to rituximab. 108 (83%) of 130 patients assigned to CT-P10 and 104 (81%) of 128 assigned to rituximab achieved an overall response by month 7 (treatment difference estimate 1-8%; 90% CI 6-43 to 10 20). Therapeutic equivalence was shown (90% CIs were within the prespecified margin of 17%). The most common grade 3 or 4 treatment-emergent adverse events were decreased neutrophil count (two grade 3 in the CT-P10 group) and neutropenia (one in each group); all other grade 3 or 4 treatment-emergent adverse events occurred in one patient each. Six (5%) of 130 patients who received CT-P10 and three (2%) of 128 who received rituximab experienced at least one treatment-emergent serious adverse event.
Interpretation CT-P10 was equivalent to rituximab in terms of efficacy and was well tolerated. CT-P10 monotherapy is suggested as a new therapeutic option for patients with low-tumour-burden follicular lymphoma. Copyright (C) 2018 Elsevier Ltd. All rights reserved.
Filiaciones:
Ogura, M:
Kasugai Municipal Hosp, Dept Haematol & Oncol, Kasugai, Aichi, Japan
Fujita Med Univ, Sch Med, Toyoake, Aichi, Japan
:
Hosp Badalona Germans Trias & Pujol, Josep Carreras Leukaemia Res Inst, Catalan Inst Oncol, Hematol Dept, Badalona, Spain
Cho, SG:
Catholic Univ Korea, Seoul St Marys Hosp, Catholic Blood & Marrow Transplantat Ctr, Dept Hematol, Seoul, South Korea
Nakazawa, H:
Shinshu Univ, Sch Med, Dept Hematol, Matsumoto, Nagano, Japan
Suzumiya, J:
Shimane Univ Hosp, Innovat Canc Ctr Oncol Hematol, Izumo, Shimane, Japan
Tumyan, G:
NN Blokhin Russian Canc Res Ctr, Div Hematol & Bone Marrow Transplantat, Moscow, Russia
Kim, JS:
Yonsei Univ, Severance Hosp, Coll Med, Dept Internal Med, Seoul, South Korea
Lennard, A:
Newcastle Univ, Northern Inst Canc Care, Newcastle Upon Tyne, Tyne & Wear, England
Mariz, J:
Portuguese Inst Oncol, Dept Oncohematol, Porto, Portugal
Ilyin, N:
Minist Hlth Russian Federat, Russian Res Ctr Radiol & Surg Technol, St Petersburg, Russia
Jurczak, W:
Jagiellonian Univ, Dept Haematol, Krakow, Poland
Martinez, AL:
Hosp Arnau Vilanova, Dept Hematol, Valencia, Spain
Samoilova, O:
Nizhniy Novgorod Reg Clin Hosp, Dept Hematol, Nizhnii Novgorod, Russia
Zhavrid, E:
NN Alexandrov Republican Sci & Pract Ctr Oncol &, Minsk, BELARUS
Ruiz, EY:
Univ La Frontera, Dept Internal Med, Temuco, Chile
Trneny, M:
Charles Univ Prague, Gen Hosp Prague, Dept Med, Prague, Czech Republic
Popplewell, L:
City Hope Natl Med Ctr, Toni Stephenson Lymphoma Ctr, Duarte, CA USA
City Hope Natl Med Ctr, Dept Hematol & Hematopoiet Cell Transplantat, Duarte, CA USA
Coiffier, B:
Hosp Civils Lyon, Dept Hematol, Lyon, France
Buske, C:
Univ Hosp Ulm, Comprehens Canc Ctr Ulm, Ulm, Germany
Kim, WS:
Sungkyunkwan Univ, Samsung Med Ctr, Sch Med, Div Hematol & Oncol,Dept Med, Seoul, South Korea
Lee, SJ:
Celltrion Inc, Incheon, South Korea
Lee, SY:
Celltrion Inc, Incheon, South Korea
Bae, YJ:
Celltrion Inc, Incheon, South Korea
Kwak, LW:
City Hope Natl Med Ctr, Toni Stephenson Lymphoma Ctr, Duarte, CA USA
City Hope Natl Med Ctr, Dept Hematol & Hematopoiet Cell Transplantat, Duarte, CA USA
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