SAN DIEGO—Substituting obinutuzumab for rituximab in combination with CHOP chemotherapy does not improve outcomes in patients with previously untreated diffuse large B-cell lymphoma (DLBCL), according to a study presented at the 2016 ASH Annual Meeting.
In this phase 3 trial, known as GOYA, researchers compared obinutuzumab plus CHOP (G-CHOP) to rituximab plus CHOP (R-CHOP) in patients with previously untreated DLBCL.
There were no significant differences between the treatment arms with regard to response rates, progression-free survival (PFS), or overall survival (OS).
In addition, grade 3-5 adverse events (AEs) and serious AEs were more common with G-CHOP than with R-CHOP.
“Rituximab plus CHOP remains the standard of care in this setting,” said study investigator Umberto Vitolo, MD, of the Universitaria Città della Salute e della Scienza di Torino in Torino, Italy.
“Further analyses of the data from this trial will inform and shape the direction of future research activities in DLBCL.”
Dr Vitolo presented results from GOYA at ASH as abstract 470.
Obinutuzumab is a glycoengineered, type II, anti-CD20 monoclonal antibody said to have greater direct cell death induction and antibody-dependent cellular cytotoxicity/phagocytosis activity than rituximab.
In the phase 2 GATHER trial, G-CHOP demonstrated manageable toxicity and promising preliminary efficacy in patients with advanced, untreated DLBCL.
So with the phase 3 GOYA trial, researchers wanted to compare G-CHOP to R-CHOP in DLBCL. The trial enrolled 1418 patients (median age 62) with previously untreated DLBCL.
Patients from 207 centers around the world were randomized to receive eight 21-day cycles of obinutuzumab at 1000 mg intravenously on days 1, 8, and 15 in cycle 1 and day 1 in cycles 2 to 8 (n=706) or rituximab at 375 mg/m2 intravenously on day 1 (n=712) in combination with 6 or 8 cycles of CHOP. Preplanned radiotherapy was allowed for bulky or extranodal disease.
Dr Vitolo said baseline characteristics were well balanced between the 2 treatment arms. Cell-of-origin distribution, as assessed by gene-expression profiling, was similar in both arms.
Virtually all (88%) of the patients received more than 90% of the planned cumulative dose of chemotherapy. Antibody dose delays were more common in the G-CHOP arm.
Efficacy
The median follow-up was 29 months.
For the primary endpoint of investigator-assessed PFS, there was no significant difference between the G-CHOP and R-CHOP arms. The 3-year PFS was 69.6% for G-CHOP and 66.9% for R-CHOP (hazard ratio [HR]=0.92, P=0.3868).
There were no clinically meaningful differences observed between the treatment arms in terms of secondary endpoints, including OS, end-of-treatment overall response rate, and complete response rate, with or without PET scanning.
At the end of treatment, the overall response rates, according to CT and PET, were 77.9% in the R-CHOP arm and 77.4% in the G-CHOP arm. The complete response rates were 59.5% and 56.7%, respectively.
The 3-year OS rate was 81.4% in the R-CHOP arm and 81.2% in the G-CHOP arm (HR=1.00, P=0.9982).
In a pre-specified subgroup analysis of investigator-assessed PFS, there was a slight trend toward improved PFS in favor of G-CHOP for patients with GCB DLBCL, with a 3-year PFS of 79% vs 70% for R-CHOP (HR=0.72).
Safety
No new safety signals were identified. Grade 3 or higher AEs and serious AEs were more common in the G-CHOP arm than the R-CHOP arm. The incidence of grade 3-5 AEs was 73.7% and 64.7%, respectively. The incidence of serious AEs was 42.6% and 37.6%, respectively.
Certain grade 3-5 AEs were more common with G-CHOP than R-CHOP, including neutropenia (46.2% vs 38.1%), infusion-related reactions (2.8% vs 0.6%), infections (19.2% vs 15.5%), and thrombocytopenia 4.4% vs 1.4%).
AEs resulting in withdrawal from treatment and AEs with fatal outcomes were slightly more common with G-CHOP than with R-CHOP. AEs leading to withdrawal occurred in 11.9% and 8.5% of patients, respectively.
Fatal AEs (listed by preferred term) in the G-CHOP arm included septic shock (n=6, 0.9%), pneumonia (n=5, 0.7%), death (n=3, 0.4%), pulmonary embolism (n=2, 1.3%), and cerebrovascular accident (n=2, 0.3%).
Fatal AEs in the R-CHOP arm included pneumonia (n=6, 0.9%), sepsis (n=3, 0.4%), cerebrovascular accident (n=2, 0.3%), and death (n=2, 0.3%).
