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Clinical Trial
. 2019 Jul 20;37(21):1790-1799.
doi: 10.1200/JCO.18.01994. Epub 2019 Apr 2.

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

Nancy L Bartlett  1 , Wyndham H Wilson  2 , Sin-Ho Jung  3 , Eric D Hsi  4 , Matthew J Maurer  5 , Levi D Pederson  5 , Mei-Yin C Polley  5 , Brandelyn N Pitcher  3 , Bruce D Cheson  6 , Brad S Kahl  1 , Jonathan W Friedberg  7 , Louis M Staudt  2 , Nina D Wagner-Johnston  1 , Kristie A Blum  8 , Jeremy S Abramson  9 , Nishitha M Reddy  10 , Jane N Winter  11 , Julie E Chang  12 , Ajay K Gopal  13 , Amy Chadburn  14 , Susan Mathew  14 , Richard I Fisher  15 , Kristy L Richards  16 , Heiko Schöder  17 , Andrew D Zelenetz  17 , John P Leonard  14
Affiliations
Clinical Trial

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

Nancy L Bartlett et al. J Clin Oncol. .

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.

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Conflict of interest statement

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Figures

FIG 1.
FIG 1.
CONSORT diagram. ANC, absolute neutrophil count; CALGB, Cancer and Leukemia Group B; DA-EPOCH-R, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab; DLBCL, diffuse large B-cell lymphoma; FNA, fine-needle aspirate; LVEF, left ventricular ejection fraction; NHL, non-Hodgkin lymphoma; NOS, not otherwise specified; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.
FIG 2.
FIG 2.
Progression-free survival (PFS) by treatment arm. Kaplan-Meier PFS estimate of all patients by treatment arm in years since random assignment. There was no statistically significant difference in PFS between arms (P = .6519). DA-EPOCH-R, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab; HR, hazard ratio; KM Est, KM, Kaplan-Meier estimate; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.
FIG 3.
FIG 3.
Overall survival (OS) by treatment arm. Kaplan-Meier OS estimate of all patients by treatment arm in years since random assignment. The 5-year OS was similar between the R-CHOP and DA-EPOCH-R arms (P = .6414). DA-EPOCH-R, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab; HR, hazard ratio; KM Est, KM, Kaplan-Meier estimate; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.
FIG 4.
FIG 4.
Progression-free survival (PFS) by subset analysis. Post hoc comparison of PFS by arm in subgroups of standard clinical features, including age, LDH level, Eastern Cooperative Oncology Group performance status, extranodal disease, stage, and IPI risk group. PFS was higher in the DA-EPOCH-R arm in the highest risk IPI (4-5) subgroup (unadjusted P = .0524). No meaningful difference in PFS between arms for any of the other subgroups was demonstrated. DA-EPOCH-R, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab; HR, hazard ratio; IHC, immunohistochemistry; IPI, International Prognostic Index; LDH, lactate dehydrogenase; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.
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Comment in

  • Reply to T.M. Weis et al.
    Bartlett NL, Wilson WH, Leonard JP. Bartlett NL, et al. J Clin Oncol. 2019 Nov 1;37(31):2953. doi: 10.1200/JCO.19.01617. Epub 2019 Sep 18. J Clin Oncol. 2019. PMID: 31532721 No abstract available.
  • Dosing Vincristine in Dose-Adjusted EPOCH-R: To Cap or Not to Cap?
    Weis TM, Perissinotti AJ, Nachar VR, Brown AM, Phillips TJ, Marini BL. Weis TM, et al. J Clin Oncol. 2019 Nov 1;37(31):2952. doi: 10.1200/JCO.19.01259. Epub 2019 Sep 18. J Clin Oncol. 2019. PMID: 31532723 No abstract available.

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