Phase III randomized intergroup trial of CHOP plus rituximab compared with CHOP chemotherapy plus (131)iodine-tositumomab for previously untreated follicular non-Hodgkin lymphoma: SWOG S0016

Abstract

Purpose: Advanced follicular lymphomas (FL) are considered incurable with conventional chemotherapy and there is no consensus on the best treatment approach. Southwest Oncology Group (SWOG) and Cancer and Leukemia Group B compared the safety and efficacy of two immunochemotherapy regimens for FL in a phase III randomized intergroup protocol (SWOG S0016) that enrolled 554 patients with previously untreated, advanced-stage FL between March 1, 2001, and September 15, 2008.

Patients and methods: Patients were eligible for the study if they had advanced-stage (bulky stage II, III, or IV) evaluable FL of any grade (1, 2, or 3) and had not received previous therapy. In one arm of the study, patients received six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy at 3-week intervals with six doses of rituximab (CHOP-R). In another arm of the study, patients received six cycles of CHOP followed by consolidation with tositumomab/iodine I-131 tositumomab radioimmunotherapy (RIT).

Results: After a median follow-up period of 4.9 years, the 2-year estimate of progression-free survival (PFS) was 76% on the CHOP-R arm and 80% on the CHOP-RIT arm (P = .11). The 2-year estimate of overall survival (OS) was 97% on the CHOP-R arm and 93% on the CHOP-RIT arm (P = .08).

Conclusion: There was no evidence of a significant improvement in PFS comparing CHOP-RIT with CHOP-R. However, PFS and OS were outstanding on both arms of the study. Future studies are needed to determine the potential benefits of combining CHOP-R induction chemotherapy with RIT consolidation and/or extended rituximab maintenance therapy.

Trial registration: ClinicalTrials.gov NCT00006721.

Fig 1.

Progression-free survival (PFS) and overall survival (OS) of 90 eligible patients with advanced-stage follicular non-Hodgkin lymphoma treated with six cycles of cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy followed by tositumomab/¹³¹I-tositumomab on Southwest Oncology Group protocol S9911. FU, follow-up.

Fig 2.

Design of Southwest Oncology Group Protocol S0016. (A) Schema for patients randomly assigned to six cycles of cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy with six doses of rituximab (CHOP-R). (B) Schema for patients randomly assigned to six cycles of cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy followed by consolidation with tositumomab/¹³¹I-tositumomab radioimmunotherapy (CHOP-RIT). IV, intravenous.

Fig 3.

CONSORT diagram illustrating patient flow on Southwest Oncology Group protocol S0016. AE, adverse event; CHOP-R, cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy with rituximab; CHOP-RIT, cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy followed by tositumomab/¹³¹I-tositumomab radioimmunotherapy.

Fig 4.

(A) Progression-free and (B) overall survival of 532 patients with advanced-stage follicular lymphoma randomly assigned to either six cycles of cyclophosphamide, doxorubicin, vincristine, prednisone plus rituximab (CHOP-R) or six cycles of cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy followed by consolidation with tositumomab/¹³¹I-tositumomab radioimmunotherapy (CHOP-RIT). FU, follow-up.