The evidence of Obinutuzumab-CVP is mostly derived from the multicentre phase 3, open labelled GALLIUM study, which compared the combination of obinutuzumab-chemotherapy (G-chemo) versus rituximab-chemotherapy (R-chemo) in previously untreated advanced stage follicular lymphoma. It has limitations when it comes to comparing the different chemotherapy backbones as patients were not randomly assigned to each chemotherapy backbone.r
1202 patients were randomised 1:1 to receive either G-chemo or R-chemo. The choice of chemotherapy regimen was left to investigators discretion between cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); cyclophosphamide, vincristine, and prednisone (CVP); or bendamustine. Responding patients (complete or partial response at the end of induction) continued on to receive maintenance treatment with the same antibody treatment every 2 months for 2 years, until disease progression or withdrawal from the trial.r
Primary end point was progression free survival (PFS) and secondary end points included overall response (OR) rate at the end of induction therapy, event-free survival, disease-free survival, duration of response, overall survival (OS), time to new anti-lymphoma treatment (TTNAT), and safety.r
Baseline data of each chemotherapy backbone showed some notable differences between groups. More patients receiving CHOP were in the FLIPI high-risk group (47% compared to 40% in bendamustine and 35% in CVP). Patients in the bendamustine arm had more comorbidities (24% with Charlson comorbid index score ≥1 vs 17% [CHOP] and 19% [CVP]). There was a higher population of patients ≥ 80years in the bendamustine and CVP group (3% in both groups) compared to CHOP (1%).r
A secondary analysis of the GALLIUM study was conducted to evaluate the prognostic value of PET-CT responses after first-line immunochemotherapy in the GALLIUM study. As per protocol, during the trial, PET scans (mandatory in the first 170 patients enrolled at sites with available PET facilities, and optional thereafter), acquired at baseline and end of induction, were assessed prospectively by investigators and an independent review committee (IRC). Pet scans were done in 669 (65%) of 1029 patients enrolled after July 26, 2011, at 103 of the 177 recruiting centres. Results from the investigators and IRC found that PET is a better imaging modality with better predictive ability than contrast-enhanced CT for response assessment.r
Efficacy
After a median follow up of 41.1 months, there was a significant increase in PFS in patients treated with G-chemo compared to R-chemo (HR, 0.68; 95% CI, 0.54 to 0.87; P =.0016). No OS benefit was seen between these 2 groups. TTNAT was slightly better in the G-chemo group with 14% needing the next line of treatment compared to 20% in the R-chemo group (HR 0.68, 95% CI 0.52-0.90, p=0.007). Complete or partial response rate was not significantly different between the two groups regardless of whether CT imaging or CT plus PET was used.rr
The benefit of obinutuzumab over rituximab was seen with all three chemotherapy backbones with Hazard ratios for investigator-assessed PFS of 0.63 (95% CI, 0.46 to 0.88) for bendamustine, 0.72 (0.48 to 1.10) for CHOP, and 0.79 (0.42 to 1.47) for CVP.r
© Journal of Clinical Oncology 2018
© Journal of Clinical Oncology 2018
© Journal of Clinical Oncology 2018
Toxicity
There were more patients with Grade 3-5 AEs in the G-chemo arm compared to R-chemo (75% vs 69% respectively). Within limitations, in those receiving G-chemo, there were 69% grade 3-5 AEs in the CVP arm compared to 89% in the G-CHOP arm and 69% in the G-Bendamustine arm. The higher rate in the G-CHOP arm were mainly driven by cytopenias. Infection rates were higher in the bendamustine group. r
© Journal of Clinical Oncology 2018