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

• Published in: Journal of clinical oncology Vol. 37; no. 21; pp. 1790 - 1799
• Main Authors: Bartlett, Nancy L., Wilson, Wyndham H., Jung, Sin-Ho, Hsi, Eric D., Maurer, Matthew J., Pederson, Levi D., Polley, Mei-Yin C., Pitcher, Brandelyn N., Cheson, Bruce D., Kahl, Brad S., Friedberg, Jonathan W., Staudt, Louis M., Wagner-Johnston, Nina D., Blum, Kristie A., Abramson, Jeremy S., Reddy, Nishitha M., Winter, Jane N., Chang, Julie E., Gopal, Ajay K., Chadburn, Amy, Mathew, Susan, Fisher, Richard I., Richards, Kristy L., Schöder, Heiko, Zelenetz, Andrew D., Leonard, John P.
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology 20.07.2019
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cyclophosphamide - pharmacology; Cyclophosphamide - therapeutic use; Disease-Free Survival; Doxorubicin - pharmacology; Doxorubicin - therapeutic use; Etoposide - pharmacology; Etoposide - therapeutic use; Female; Humans; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - mortality; Male; Middle Aged; Prednisone - pharmacology; Prednisone - therapeutic use; Progression-Free Survival; RAPID COMMUNICATION; Vincristine - pharmacology; Vincristine - therapeutic use; Young Adult
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.18.01994

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 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. 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; = .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; = .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 ( < .001) in the DA-EPOCH-R arm than the R-CHOP arm, including infection (16.9% 10.7%, respectively), febrile neutropenia (35.0% 17.7%, respectively), mucositis (8.4% 2.1%, respectively), and neuropathy (18.6% 3.3%, respectively). Five treatment-related deaths (2.1%) occurred in each arm. 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.