The results of the PRELUDE study (NCT00332202 trial) were published by M. Crump from the Princess Margaret Cancer Center in Toronto, and colleagues in J Clin Oncol. in July 2016. Unfortunately, the results of this trial were not as hopeful as expected.
The primary objective of this study was to compare Disease-Free Survival (DFS) with enzastaurin as maintenance therapy versus placebo in patients with Diffuse Large B-Cell Lymphoma (DLBCL) who were at a high risk of experiencing relapse after achieving a Complete Response (CR) with rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as first-line therapy. Biomarker analysis was a secondary study objective.
Here are the take home messages:
- Enzastaurin, when administered for 3 years as maintenance therapy, to patients who have achieved CR after first-line R-CHOP therapy, did not significantly improve DFS compared with placebo
- Identifying the value of specific biomarkers in predicting therapeutic response to novel targeted agents may be useful for future trials within defined subgroups of patients with DLBCL
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
Purpose: To compare disease-free survival (DFS) after maintenance therapy with the selective protein kinase C β (PKCβ) 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.
Patients and Methods: 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 PKCβ expression, with efficacy outcomes were exploratory objectives.
Results: 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 PKCβ protein expression or cell of origin and DFS or overall survival.
Conclusion: 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.
- Supported by Eli Lilly
- Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article
- Clinical trial information: NCT00332202