Crump et al found no disease-free survival benefit of maintenance therapy with the selective protein kinase Cb (PKCb) inhibitor enzastaurin in patients with diffuse large B-cell lymphoma (DLBCL) who were in complete remission and at high risk of relapse after first-line chemotherapy, according to a phase III trial reported in the Journal of Clinical Oncology.
In the double-blind trial, 758 patients from 25 countries were randomized 2:1 to receive oral enzastaurin at 500 mg daily or placebo for 3 years or until disease progression or unacceptable toxicity. Patients had to have stage II bulky or stage III to IV DLBCL and at least three International Prognostic Index risk factors at diagnosis and a complete or unconfirmed complete response after 6 to 8 cycles of R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone). The primary endpoint was disease-free survival at 3 years after the last patient entered treatment.
Median follow-up was 48 months. The hazard ratio (HR) for disease-free survival for enzastaurin vs placebo was 0.92 (P = .541). At 2 years, disease-free survival was 78% vs 75%, and overall survival was 87% vs 89%. At 4 years, disease-free survival was 70% vs 71%, and overall survival was 81% vs 82%.
No significant associations were observed between PKCb protein expression or cell of origin and disease-free or overall survival independent of the treatment group.
The investigators concluded: “Enzastaurin did not significantly improve [disease-free survival] 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.”
The study was supported by Eli Lilly.
Michael Crump, MD, of the Princess Margaret Cancer Centre, Toronto, Ontario, Canada, is the corresponding author of the Journal of Clinical Oncology article.
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