Title | 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. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Bartlett NL, Wilson WH, Jung S-H, Hsi ED, Maurer MJ, Pederson LD, Polley M-YC, Pitcher BN, Cheson BD, Kahl BS, Friedberg JW, Staudt LM, Wagner-Johnston ND, Blum KA, Abramson JS, Reddy NM, Winter JN, Chang JE, Gopal AK, Chadburn A, Mathew S, Fisher RI, Richards KL, Schoder H, Zelenetz AD, Leonard JP |
Journal | J Clin Oncol |
Volume | 37 |
Issue | 21 |
Pagination | 1790-1799 |
Date Published | 2019 07 20 |
ISSN | 1527-7755 |
Keywords | Adolescent, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Cyclophosphamide, Disease-Free Survival, Doxorubicin, Etoposide, Female, Humans, Lymphoma, Large B-Cell, Diffuse, Male, Middle Aged, Prednisone, Progression-Free Survival, Vincristine, Young Adult |
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; = .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. 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. |
DOI | 10.1200/JCO.18.01994 |
Alternate Journal | J Clin Oncol |
PubMed ID | 30939090 |
PubMed Central ID | PMC6774813 |
Grant List | U10 CA180821 / CA / NCI NIH HHS / United States U10 CA180882 / CA / NCI NIH HHS / United States U10 CA180888 / CA / NCI NIH HHS / United States UG1 CA233290 / CA / NCI NIH HHS / United States UG1 CA233270 / CA / NCI NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States U10 CA180847 / CA / NCI NIH HHS / United States U10 CA180820 / CA / NCI NIH HHS / United States P50 CA097274 / CA / NCI NIH HHS / United States U10 CA180833 / CA / NCI NIH HHS / United States U10 CA049957 / CA / NCI NIH HHS / United States U10 CA180799 / CA / NCI NIH HHS / United States P30 CA006927 / CA / NCI NIH HHS / United States UG1 CA233328 / CA / NCI NIH HHS / United States |
Related Faculty:
Amy Chadburn, M.D.