Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303.

Abstract

PURPOSE:

Alliance/CALGB 50303 (NCT00118209), an intergroup, phase III study, compared dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as frontline therapy for diffuse large B-cell lymphoma.

PATIENTS AND METHODS:

Patients received six cycles of DA-EPOCH-R or R-CHOP. The primary objective was progression-free survival (PFS); secondary clinical objectives included response rate, overall survival (OS), and safety.

RESULTS:

Between 2005 and 2013, 524 patients were registered; 491 eligible patients were included in the final analysis. Most patients (74%) had stage III or IV disease; International Prognostic Index (IPI) risk groups included 26% IPI 0 to 1, 37% IPI 2, 25% IPI 3, and 12% IPI 4 to 5. At a median follow-up of 5 years, PFS was not statistically different between the arms (hazard ratio, 0.93; 95% CI, 0.68 to 1.27; P = .65), with a 2-year PFS rate of 78.9% (95% CI, 73.8% to 84.2%) for DA-EPOCH-R and 75.5% (95% CI, 70.2% to 81.1%) for R-CHOP. OS was not different (hazard ratio, 1.09; 95% CI, 0.75 to 1.59; P = .64), with a 2-year OS rate of 86.5% (95% CI, 82.3% to 91%) for DA-EPOCH-R and 85.7% (95% CI, 81.4% to 90.2%) for R-CHOP. Grade 3 and 4 adverse events were more common (P < .001) in the DA-EPOCH-R arm than the R-CHOP arm, including infection (16.9% v 10.7%, respectively), febrile neutropenia (35.0% v 17.7%, respectively), mucositis (8.4% v 2.1%, respectively), and neuropathy (18.6% v 3.3%, respectively). Five treatment-related deaths (2.1%) occurred in each arm.

CONCLUSION:

In the 50303 study population, the more intensive, infusional DA-EPOCH-R was more toxic and did not improve PFS or OS 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.

• Authors: Nancy L Bartlett, Wyndham H Wilson, Sin-Ho Jung, Eric D Hsi, Matthew J Maurer, Levi D Pederson, Mei-Yin C Polley, Brandelyn N Pitcher, Bruce D Cheson, Brad S Kahl, Jonathan W Friedberg, Louis M Staudt, Nina D Wagner-Johnston, Kristie A Blum, Jeremy S Abramson, Nishitha M Reddy, Jane N Winter, Julie E Chang, Ajay K Gopal, Amy Chadburn, Susan Mathew, Richard I Fisher, Kristy L Richards, Heiko Schöder, Andrew D Zelenetz, John P Leonard
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 37 Issue 21 Pg. 1790-1799 (07 20 2019) ISSN: 1527-7755 [Electronic] United States
• PMID: 30939090 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Vincristine
• Etoposide
• Doxorubicin
• Cyclophosphamide
• Prednisone

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• Cyclophosphamide (pharmacology, therapeutic use)
• Disease-Free Survival
• Doxorubicin (pharmacology, therapeutic use)
• Etoposide (pharmacology, therapeutic use)
• Female
• Humans
• Lymphoma, Large B-Cell, Diffuse (drug therapy, mortality)
• Male
• Middle Aged
• Prednisone (pharmacology, therapeutic use)
• Progression-Free Survival
• Vincristine (pharmacology, therapeutic use)
• Young Adult