Etopo the mornin’ to ya.

Top Line: R-CHOP is the gold standard systemic therapy regimen for diffuse large B-cell lymphoma (DLBCL).
The Study: R-EPOCH is a twist that adds etoposide and alters drug administration. The idea is to maximize dose intensity and drug exposure while limiting cardiac toxicity, but it’s never been put head to head with R-CHOP in the front-line setting for DLBCL. Until now. In Intergroup/CALGB 50303, nearly 500 patients with stage II-IV DLBCL and stage I-IV primary mediastinal DLBCL were randomized to 6 cycles of R-CHOP or R-EPOCH. Patients with multiple extranodal sites, elevated LDH, or marrow involvement also received CNS prophylaxis with intrathecal methotrexate. Almost 75% of patients had stage III/IV disease with nearly 50% having stage IV disease. At 5 years, there was no difference in progression-free (66-68%) nor overall survival. Both the primary mediastinal and double-hit (i.e., the worst) populations in this trial were fairly small, and there was no suggestion of a dramatic difference in outcome between arms. In fact, among multiple subgroup analyses, etoposide improved progression only in those with high IPI scores, although this still didn’t result in improved survival. What was significantly higher with R-EPOCH? Grade 3+ toxicity, which increased from 78 → 98%. Ongoing molecular trials will hopefully better clarify which, if any, subgroups of DLBCL benefit from the addition of etoposide.
Bottom Line: R-EPOCH applied broadly to patients with DLBCL does not improve outcomes. | Bartlett, J Clin Oncol 2019


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