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

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 (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 34

Pages Range: 2484-92

Journal Issue: 21

DOI: 10.1200/JCO.2015.65.7171

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.

Authors with CRIS profile

Involved external institutions

Mayo Clinic United States (USA) (US) British Columbia Cancer Agency Canada (CA) University of Wisconsin - Madison United States (USA) (US) Eli Lilly and Company United States (USA) (US) Cleveland Clinic United States (USA) (US) China Medical University (CMU) / 中国医科大学 China (CN) National Cancer Centre Singapore (NCCS) Singapore (SG) University of Chicago United States (USA) (US) University of California Los Angeles (UCLA) United States (USA) (US) Universiteit Gent (UGent) / Ghent University Belgium (BE) The US Oncology Network United States (USA) (US) Central Georgia Cancer Care United States (USA) (US) Uppsala University Hospital / Akademiska sjukhuset Sweden (SE) Tokai University Hospital Japan (JP) Università degli studi "La Sapienza" Italy (IT) Chonnam National University Hwasun Hospital Korea, Republic of (KR) University of Texas MD Anderson Cancer Center United States (USA) (US) Helsinki University Central Hospital (HUCH) / Helsingin seudun yliopistollinen keskussairaala (HYKS) Finland (FI) University of Toronto Canada (CA) Asklepios Kliniken Germany (DE)

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.

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