No Benefit of Adding Obinutuzumab to CHOP in Previously Untreated DLBCL

August 28, 2017

Adding obinutuzumab to cyclophosphamide, doxorubicin, vincristine, and prednisone (G-CHOP) failed to improve progression-free survival compared with rituximab plus CHOP in patients with previously untreated diffuse large B-cell lymphoma.

Adding obinutuzumab to cyclophosphamide, doxorubicin, vincristine, and prednisone (G-CHOP) failed to improve progression-free survival (PFS) compared with rituximab plus CHOP (R-CHOP) in patients with previously untreated diffuse large B-cell lymphoma (DLBCL), according to the results of the phase III GOYA study published in the Journal of Clinical Oncology.

After a median follow-up of about 2.5 years, the number of investigator-assessed PFS events was similar between the two arms.

“Given the advantages of G-based therapy in patients with follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL), the lack of benefit of G-CHOP in patients with DLBCL in the GOYA study was unexpected, and the reasons for it are unclear,” wrote Umberto Vitolo, MD, of Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino in Italy, and colleagues. “This lack of benefit might simply have resulted from the differences in biologic and clinical profiles between indolent lymphoproliferative diseases, such as FL and CLL, and aggressive ones, such as DLBCL.”

Phase III studies of patients with FL or CLL treated with obinutuzumab indicated superiority of the therapy compared with rituximab, and smaller studies of patients with aggressive non-Hodgkin lymphoma including DLBCL showed that the therapy demonstrated promise.

In the GOYA study, 1,418 patients with untreated DLBCL were randomly assigned to 8 21-day cycles of obinutuzumab or rituximab plus 6 or 8 cycles of CHOP. The primary endpoint was investigator-assessed PFS.

Most patients in the study received more than 90% of the planned dose of each regimen. With a median follow-up of 29 months, there were 201 PFS events in the G-CHOP arm and 215 in the R-CHOP arm. The estimated 3-year PFS rate was 69.6% for G-CHOP and 66.9% for R-CHOP.

There were no clinically significant differences between secondary endpoints, including independently reviewed PFS, other time-to-event endpoints, and tumor response rates.

The researchers also conducted an exploratory analysis looking at disease subtype and found that patients with germinal-center B-cell–like subtype had better PFS compared with patients with activated B-cell–like subtype, regardless of treatment arm. Efficacy of the two treatments was similar across most other subgroup analyses, including for those patients who received 6 compared with 8 cycles of CHOP.

Patients assigned to G-CHOP had higher rates of grade 3 to 5 adverse events and serious adverse events. The most common adverse events were neutropenia, infusion-related reactions, nausea, and constipation.

“Of note, dose interruptions and skipped doses in cycle 1 were more frequent with G-CHOP, which reflects a higher rate of adverse events (infusion-related reactions and cytopenias),” the researchers wrote. “This might have contributed to the lack of efficacy benefit compared with R-CHOP.”