Front-Line Dose-Adjusted EPOCH-R vs R-CHOP in Diffuse Large B-Cell Lymphoma
As reported in the Journal of Clinical Oncology by Bartlett et al, the phase III intergroup Alliance/CALGB 50303 trial showed front-line DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) did not improve outcomes vs standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in diffuse large B-cell lymphoma.
In the trial, 524 patients were randomly assigned between 2005 and 2013 to 6 cycles of DA-EPOCH-R or R-CHOP. Among 491 eligible patients included in the current analysis, 241 received DA-EPOCH-R and 250 received R-CHOP. The current analysis presents clinical outcomes after a median follow-up of 5.2 years—the data cutoff was in November 2017.
Most patients (74%) had stage III or IV disease. The primary endpoint was progression-free survival.
Survival and Adverse Events
At a median follow-up of 5 years, there was no significant difference in progression-free survival in the DA-EPOCH-R vs R-CHOP groups (hazard ratio [HR] = 0.93, P = .65); progression-free survival was 78.9% vs 75.5% at 2 years and 68.0% vs 66.0% at 5 years. These findings were consistent when stratified by International Prognostic Index score. No difference in overall survival was observed (HR = 1.09, P = .64); overall survival was 86.5% vs 85.7% at 2 years and 77.5% vs 78.5% at 5 years.
Grade ≥ 3 treatment-related adverse events occurred in 98.3% of patients in the DA-EPOCH-R group vs 78.2% in the R-CHOP group (P < .001), with both grade 3 or 4 hematologic (97.5% vs 73.7%, P < .001) and nonhematologic (72.2% vs 43.2%, P < .001) adverse events being significantly more common with DA-EPOCH-R. Grade 3 or 4 adverse events that were more common in the DA-EPOCH-R group included infection (16.9% vs 10.7%), febrile neutropenia (35.0% vs 17.7%), mucositis (8.4% vs 2.1%), and neuropathy (18.6% vs 3.3%). Treatment-related deaths occurred in 5 patients (2.1%) in each group.
The investigators concluded, “In the 50303 study population, the more intensive, infusional DA-EPOCH-R was more toxic and did not improve [progression-free or overall survival] compared with R-CHOP. The more favorable results with R-CHOP compared with historical controls suggest a potential patient selection bias and may preclude generalizability of results to specific risk subgroups.”
Nancy L. Bartlett, MD, of Washington University School of Medicine in St. Louis, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute. For full disclosures of the study authors, visit jco.ascopubs.org.
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