ROCKVILLE, MarylandRituxan (rituximab) in combination with CHOP (cyclophosphamide, doxorubicin(Drug information on doxorubicin), vincristine, prednisone(Drug information on prednisone)) or other anthracycline-based chemotherapy regimens has received approval from the FDA for use as first-line treatment of diffuse large B cell non-Hodgkin's lymphoma (DLBCL) in CD20-positive patients. The drug, co-marketed by Genentech and Biogen Idec, was initially FDA approved in 1997 for the treatment of relapsed or refractory low-grade or follicular, CD20-positive, B-cell NHL.
FDA based its expanded indication on three randomized, controlled, multicenter studies of 1,854 previously untreated patients with DLBCL. "With 2 years of follow-up, more patients were alive in the Rituxan-containing vs control arms for each study," Genentech said, in announcing the drug's new approval. "In one of the studies with 5 years of follow-up, the GELA trial, R-CHOP improved overall survival by 47%, compared to CHOP alone . . . which is equivalent to a 32% decrease in the risk of death." The studies submitted to FDA were:
E4494, an NCI-supported trial led by the Eastern Cooperative Oncology Group, involved 632 patients age 60 or older with B-cell NHL grade F, G, or H (International Working Formulation), or DLBCL randomized to CHOP or Rituxan/CHOP. Progression-free survival was 1.6 years for the CHOP-only arm vs 3.1 years for the Rituxan/CHOP patients, a hazard ratio (HR) of 0.69; overall survival at 2 years was 63% and 74%, respectively (HR 0.72).
GELA/LNH 98-5, a trial of 399 DLBCL patients age 60 or older assigned to CHOP or Rituxan/CHOP, showed event-free survival (defined as the time from randomization to relapse, progression, change in therapy, or death from any cause) of 1.1 years for CHOP vs 2.9 years for Rituxan/CHOP (HR 0.60). Overall survival at 2 years was 58% and 69%, respectively (HR 0.68).
MabThera International Trial M39045 (Rituxan is marketed in Europe as MabThera) included 823 DLBCL patients age 18 to 60 randomized to receive an anthracycline-containing chemotherapy regimen alone or in combination with Rituxan. The researchers reported that the main efficacy outcome of time to treatment failure proved "not reliably estimable." However, 2-year overall survival was 86% in the chemotherapy-only arm vs 95% in the Rituxan-treated patients (HR 0.40).