Results of the phase III GOYA trial – CHOP combined with rituximab or obinutuzumab demonstrates similar PFS in patients with treatment naïve DLBCL

On 10^th August 2017, results of the phase III, multicenter, randomized, GOYA trial (NCT01287741) were published by Umberto Vitolo from Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Turin, Italy, et al. in the Journal of Clinical Oncology.

The trial aimed to investigate the efficacy of obinutuzumab (G) plus CHOP versus rituximab (R) plus CHOP in patients with treatment naïve, advanced stage, CD20+, Diffuse Large B-Cell Lymphoma (DLBCL). Overall, 1,418 patients were enrolled from 207 centers across 29 counties and were randomized at a ratio of 1:1 to either G-CHOP (n=706) or R-CHOP (n=712). The primary outcome measure of the GOYA trial was investigator-assessed PFS.

Key Highlights:

Patients and treatment:

• G: 1,000mg IV on days 1, 8, and 15 of cycle 1, and on day 1 of cycles 2–8
• R: 375mg/m² IV on day 1 of cycles 1–8
• CHOP (6–8 cycles): cyclophosphamide 750mg/m² IV day 1; doxorubicin 50mg/m² IV day 1; vincristine 1.4mg/m² IV day 1 (maximum 2.0 mg); and prednisone 100mg/day orally days 1–5
• Demographic and baseline disease characteristics were well balanced between arms (median age for both arms = 62 years)
• Completed planned treatment: G-CHOP = 587 pts; R-CHOP = 601 pts; AEs were the main reason for discontinuation in both arms
• Treatment discontinuation due to PD was nearly double with R-CHOP vs G-CHOP
• Median duration of exposure: G = 25.3 weeks (range, 1–32); R = 25.3 weeks (range, 0–32)
• Antibody dose delays:
  • At least one of ≤7 days: G-CHOP = 34.9%; R-CHOP = 30.0%
  • At least one of >7 days: G-CHOP = 13.1%; R-CHOP = 9.1%
• Unplanned anti-lymphoma therapy before disease progression administered to 49 G-CHOP and 54 R-CHOP pts
• Number of pts who received radiotherapy:
  • For residual disease after study treatment completion: G-CHOP = 9; R-CHOP = 14
  • After disease progression: G-CHOP = 102; R-CHOP = 125

Efficacy:

• Median observation = 29 months
• Number of investigator-assessed PFS events: G-CHOP = 201 (28.5%); R-CHOP = 215 (30.2%; HR, 0.92; 95% CI, 0.76–1.11; P = 0.3868)
• Estimated 3-year PFS: G-CHOP = 69.6%; R-CHOP = 66.9%
• No significant difference between arms was found for secondary endpoints, which included OS, EFS, DFS, and time to next anti-lymphoma therapy
• Efficacy of both arms was similar across selected patient subgroups

Safety:

• Proportion of pts who experienced ≥1 AE of any grade: G-CHOP = 97.0%; R-CHOP = 93.5%
• The most frequent AEs in the G-CHOP and R-CHOP arms = neutropenia (48.3% vs 7%), Infusion-Related Reactions (IRRs; 36.1% vs 23.5%), nausea (29.4% vs 28.3%), and constipation (23.4% vs 24.5%)
• Grade 3–5 AEs were more frequent with G-CHOP (73.7%) compared to R-CHOP (64.7%)
• The most common grade 3–5 AEs in the G-CHOP and R-CHOP arms = neutropenia (46.2% vs 1%), infections (19.2% vs 15.5%), febrile neutropenia (17.5% vs 15.2%), and leukopenia (13.6% vs 10.1%)
• SAEs were more frequent with G-CHOP (42.6%) compared to R-CHOP (37.6%)
• Rates of hepatitis B reactivation were higher with G-CHOP (2.3%) versus R-CHOP (0.9%)
• A higher proportion of pts discontinued ≥1 components of study treatment due to an AE in the G-CHOP arm (n=84, 11.9%) versus the R-CHOP arm (n=60, 8.5%)
• Fatal AEs: G-CHOP = 5.8% (41/704 pts); R-CHOP = 4.3% (30/703 pts)

Overall, CHOP combined with G or R achieved similar efficacy for PFS, as well as other secondary time-to-event end points. The authors also stated that “no new safety signals were identified”; however, infections, neutropenia, IRRs, cardiac events, thrombocytopenia, and hemorrhagic events of any grade, in addition to grade 3–5 AEs and SAEs, were more common with G-CHOP compared to R-CHOP.

Back in June, during this year’s International Conference on Malignant Lymphoma (ICML), we spoke with Professor Marek Trněný from Charles University Hospital, Prague, Czech Republic, about the GOYA trial; watch here.

Abstract:

Purpose Rituximab (R) plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy is the standard of care in previously untreated diffuse large B-cell lymphoma (DLBCL). Obinutuzumab (G) is a glycoengineered, type II, anti-CD20 monoclonal antibody. GOYA was a randomized phase III study that compared G-CHOP with R-CHOP in patients with previously untreated advanced-stage DLBCL. Methods Patients (N = 1,418) were randomly assigned to receive eight 21-day cycles of G (n = 706) or R (n = 712), plus six or eight cycles of CHOP. Primary end point was investigator-assessed progression-free survival (PFS). Results After median observation of 29 months, the number of investigator-assessed PFS events was similar between G (201; 28.5%) and R (215; 30.2%), stratified hazard ratio was 0.92 (95% CI, 0.76 to 1.11; P = .39), and 3-year PFS rates were 70% and 67%, respectively. Secondary end points of independently reviewed PFS, other time-to-event end points, and tumor response rates were similar between arms. In exploratory subgroup analyses, patients with germinal-center B cell-like subtype had a better PFS than did patients with activated B cell-like subtype, irrespective of treatment. Frequencies of grade 3 to 5 adverse events (AEs; 73.7% v 64.7%, respectively) and serious AEs (42.6% v 37.6%, respectively) were higher with G-CHOP compared with R-CHOP. Fatal AE frequencies were 5.8% for G-CHOP and 4.3% for R-CHOP. The most common AEs were neutropenia (G-CHOP, 48.3%; R-CHOP, 40.7%), infusion-related reactions (G-CHOP, 36.1%; R-CHOP, 23.5%), nausea (G-CHOP, 29.4%; R-CHOP, 28.3%), and constipation (G-CHOP, 23.4%; R-CHOP, 24.5%). Conclusion G-CHOP did not improve PFS compared with R-CHOP in patients with previously untreated DLBCL.