Randomized, Double-Blind, Phase III Trial of Enzastaurin Versus Placebo in Patients Achieving Remission After First-Line Therapy for High-Risk Diffuse Large B-Cell Lymphoma

Journal article


Publication Details

Author(s): Crump M, Leppa S, Fayad L, Lee JJ, Di Rocco A, Ogura M, Hagberg H, Schnell F, Rifkin R, Mackensen A, Offner F, Pinter-Brown L, Smith S, Tobinai K, Yeh SP, Hsi ED, Tuan Nguyen , Shi P, Hahka-Kemppinen M, Thornton D, Lin B, Kahl B, Schmitz N, Savage KJ, Habermann T
Journal: Journal of Clinical Oncology
Publication year: 2016
Volume: 34
Journal issue: 21
Pages range: 2484-92
ISSN: 0732-183X


Abstract


To compare disease-free survival (DFS) after maintenance therapy with the selective protein kinase C ? (PKC?) inhibitor, enzastaurin, versus placebo in patients with diffuse large B-cell lymphoma (DLBCL) in complete remission and with a high risk of relapse after first-line therapy.This multicenter, phase III, randomized, double-blind, placebo-controlled trial enrolled patients who were at high risk of recurrence after rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Patients (N = 758) with stage II bulky or stage III to IV DLBCL, three or more International Prognostic Index risk factors at diagnosis, and a complete response or unconfirmed complete response after 6 to 8 cycles of R-CHOP were assigned 2:1 to receive oral enzastaurin 500 mg daily or placebo for 3 years or until disease progression or unacceptable toxicity. Primary end point was DFS 3 years after the last patient entered treatment. Correlative analyses of biomarkers, including cell of origin by immunohistochemistry and PKC? expression, with efficacy outcomes were exploratory objectives.After a median follow-up of 48 months, DFS hazard ratio for enzastaurin versus placebo was 0.92 (95% CI, 0.689 to 1.216; two-sided log-rank P = .541; 4-year DFS, 70% v 71%, respectively). Independent of treatment, no significant associations were observed between PKC? protein expression or cell of origin and DFS or overall survival.Enzastaurin did not significantly improve DFS in patients with high-risk DLBCL after achieving complete response to R-CHOP. Achievement of a complete response may have abrogated the prognostic significance of cell of origin by immunohistochemistry.



FAU Authors / FAU Editors

Mackensen, Andreas Prof. Dr.
Lehrstuhl für Innere Medizin V


External institutions with authors

Asklepios Kliniken
British Columbia Cancer Agency
Central Georgia Cancer Care
China Medical University (CMU) / 中国医科大学
Chonnam National University Hwasun Hospital
Cleveland Clinic
Eli Lilly and Company
Helsinki University Central Hospital (HUCH) / Helsingin seudun yliopistollinen keskussairaala (HYKS)
Mayo Clinic
National Cancer Centre Singapore (NCCS)
The US Oncology Network
Tokai University Hospital
Università degli studi "La Sapienza"
Universiteit Gent (UGent) / Ghent University
University of California Los Angeles (UCLA)
University of Chicago
University of Texas MD Anderson Cancer Center
University of Toronto
University of Wisconsin - Madison
Uppsala University Hospital / Akademiska sjukhuset


How to cite

APA:
Crump, M., Leppa, S., Fayad, L., Lee, J.J., Di Rocco, A., Ogura, M.,... Habermann, T. (2016). Randomized, Double-Blind, Phase III Trial of Enzastaurin Versus Placebo in Patients Achieving Remission After First-Line Therapy for High-Risk Diffuse Large B-Cell Lymphoma. Journal of Clinical Oncology, 34(21), 2484-92. https://dx.doi.org/10.1200/JCO.2015.65.7171

MLA:
Crump, Michael, et al. "Randomized, Double-Blind, Phase III Trial of Enzastaurin Versus Placebo in Patients Achieving Remission After First-Line Therapy for High-Risk Diffuse Large B-Cell Lymphoma." Journal of Clinical Oncology 34.21 (2016): 2484-92.

BibTeX: 

Last updated on 2019-22-07 at 07:35