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.

TitleDose-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 TypeJournal Article
Year of Publication2019
AuthorsBartlett 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
JournalJ Clin Oncol
Volume37
Issue21
Pagination1790-1799
Date Published2019 07 20
ISSN1527-7755
KeywordsAdolescent, 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.

DOI10.1200/JCO.18.01994
Alternate JournalJ Clin Oncol
PubMed ID30939090
PubMed Central IDPMC6774813
Grant ListU10 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
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