Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2020 Jun 6;13(1):71.
doi: 10.1186/s13045-020-00900-7.

A randomized, open-label, Phase III study of obinutuzumab or rituximab plus CHOP in patients with previously untreated diffuse large B-Cell lymphoma: final analysis of GOYA

Laurie H Sehn  1 , Maurizio Martelli  2 , Marek Trněný  3 , Wenxin Liu  4 , Christopher R Bolen  5 , Andrea Knapp  6 , Deniz Sahin  6 , Gila Sellam  6 , Umberto Vitolo  7
Affiliations
Clinical Trial

A randomized, open-label, Phase III study of obinutuzumab or rituximab plus CHOP in patients with previously untreated diffuse large B-Cell lymphoma: final analysis of GOYA

Laurie H Sehn et al. J Hematol Oncol. .

Abstract

Background: Rituximab (R) plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) is the current standard therapy for diffuse large B cell lymphoma (DLBCL). Obinutuzumab (G), a glycoengineered, type II anti-CD20 monoclonal antibody, has shown activity and an acceptable safety profile when combined with CHOP (G-CHOP) in patients with advanced DLBCL. We present the final analysis results of the Phase III GOYA study (NCT01287741), which compared the efficacy and safety of G-CHOP versus R-CHOP in patients with previously untreated DLBCL.

Methods: Patients aged ≥ 18 years with previously untreated advanced DLBCL were randomly assigned to receive eight 21-day cycles of R or G, plus six or eight cycles of CHOP. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival, other time-to-event endpoints, and safety; investigator-assessed PFS by cell of origin subgroup was an exploratory endpoint.

Results: A total of 1418 patients were randomized, with 1414 included in this final analysis (G-CHOP, N = 704; R-CHOP, N = 710). Five-year PFS rates were 63.8% and 62.6% for G-CHOP and R-CHOP, respectively (stratified hazard ratio 0.94, 95% CI 0.78-1.12; p = 0.48). The results of the secondary efficacy endpoints did not show a benefit of G-CHOP over R-CHOP. In the exploratory analysis, a trend towards benefit with G-CHOP over R-CHOP was apparent in the patients with germinal center B cell DLBCL. The safety profile of G-CHOP was as expected, and no new safety signals were observed. More grade 3-5 (75.1% vs 65.8%), serious (44.4% vs 38.4%), and fatal (6.1% vs 4.4%) adverse events (AEs) were observed in the G-CHOP arm compared with the R-CHOP arm, respectively, with the most common fatal AEs being infections. A higher incidence of late-onset neutropenia occurred in the G-CHOP arm (8.7%) versus the R-CHOP arm (4.9%).

Conclusions: The final analysis, similar to the primary analysis, did not show a PFS benefit of G-CHOP over R-CHOP in previously untreated patients with DLBCL. The results of the secondary endpoints were consistent with the primary endpoint. Further exploratory analyses and investigation of biomarkers are ongoing.

Keywords: Diffuse large B cell lymphoma; Immunochemotherapy; Obinutuzumab; Outcomes; Rituximab.

PubMed Disclaimer

Conflict of interest statement

C.B is employed by Genentech, Inc. and has equity ownership interests (including stock options) in F. Hoffmann-La Roche. A.K and W.L are employed by F. Hoffmann-La Roche. M.M has received honoraria from F. Hoffmann-La Roche, Celgene, Janssen, Sandoz, Novartis, Gilead, and Servier and is a member of an entity’s Board of Directors or advisory committees for F. Hoffmann-La Roche, Celgene, Janssen, Sandoz, Novartis, and Gilead. D.S and G.S are employed by and have equity ownership interests (including stock options) for F. Hoffmann-La Roche. L.S has provided consultancy (including expert testimony) for F. Hoffmann-La Roche, Genentech, Inc., AbbVie, Amgen, Apobiologix, AstraZeneca, Acerta, Celgene, Gilead, Janssen, Kite, Karyopharm, Lundbeck, Merck, Morphosys, Seattle Genetics, Teva, Takeda, TG Therapeutics, Verastem; has received research funding from F. Hoffmann-La Roche and Genentech, Inc.; and has received honoraria from F. Hoffmann-La Roche, Genentech, Inc., AbbVie, Amgen, Apobiologix, AstraZeneca, Acerta, Celgene, Gilead, Janssen, Kite, Karyopharm, Lundbeck, Merck, MorphoSys, Seattle Genetics, Teva, Takeda, TG Therapeutics, Verastem. M.T provides consultancy (including expert testimony) for Takeda, Bristol-Myers Squibb, Incyte, AbbVie, Amgen, F. Hoffmann-La Roche, Gilead Sciences, Janssen, Celgene, and MorphoSys and has received honoraria from Janssen, Gilead Sciences, Takeda, Bristol-Myers Squibb, Amgen, AbbVie, F. Hoffmann-La Roche, MorphoSys, and Incyte. U.V is part of the speaker’s bureau for Celgene, F. Hoffmann-La Roche, Janssen, Gilead, AbbVie, and Novartis and a member of advisory committees for Janssen, Celgene, Kite, Juno Therapeutics, Gilead, and Novartis.

Figures

Fig. 1
Fig. 1
Patient disposition from the final analysis of the GOYA trial. aOverall, 1418 patients were randomized (G-CHOP arm: N = 706 and R-CHOP arm: N = 712) to the study; however, due to a serious Good Clinical Practice non-compliance at a single site, data from all 4 patients enrolled at the site (two patients in each arm) were excluded from the final analysis. bA patient was considered to have completed the treatment if they received all 8 cycles of study treatment. cThe end of the study was defined as the last patient’s last visit and occurred at approximately 6.5 years (78 months) after the first patient was enrolled to allow all patients to have ≥ 3 years of follow-up post-treatment. G-CHOP, obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; R-CHOP, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone
Fig. 2
Fig. 2
Kaplan–Meier estimates of PFS by treatment group and OS by treatment group. a Investigator-assessed PFS (primary endpoint) by treatment (ITT population), in which no significant difference was found for G-CHOP compared with R-CHOP. b OS by treatment (ITT population), which showed no significant difference in survival between treatment groups. *Stratified by planned number of CHOP cycles and IPI score. CI, confidence interval; G-CHOP, obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; ITT, intent-to-treat; HR, hazard ratio; PFS, progression-free survival; OS, overall survival; R-CHOP, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone
Fig. 3
Fig. 3
Forest plot of unstratified HRs for investigator-assessed PFS by treatment group and patient subgroup. CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; G-CHOP, obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; HR, hazard ratio; IPI, International Prognostic Index; KM, Kaplan–Meier; R-CHOP, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone
Fig. 4
Fig. 4
Kaplan–Meier estimates of PFS by COO status by treatment group. a Investigator-assessed PFS by COO with G-CHOP, where GCB appeared to have a better outcome compared with ABC and unclassified subgroups. b Investigator-assessed PFS by COO with R-CHOP, where GCB also appeared to have a better outcome versus ABC and unclassified subgroups. ABC, activated B cell; COO, cell of origin; GCB, germinal center B cell; G-CHOP, obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; PFS, progression-free survival; OS, overall survival; R-CHOP, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone
See this image and copyright information in PMC

References

    1. Coiffier B, Lepage E, Brière J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-Cell lymphoma. N Engl J Med. 2002;346(4):235–242. doi: 10.1056/NEJMoa011795. - DOI - PubMed
    1. Tilly H, Gomes da Silva M, Vitolo U, Jack A, Meignan M, Lopez-Guillermo A, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 5):v116–v125. doi: 10.1093/annonc/mdv304. - DOI - PubMed
    1. NCCN Clinical Practice Guidelines in oncology: B-Cell Lymphomas, version 7. 2019 [Accessed 16 January 2020]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf.
    1. Sehn LH, Gascoyne RD. Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity. Blood. 2015;125(1):22–32. doi: 10.1182/blood-2014-05-577189. - DOI - PubMed
    1. Herter S, Herting F, Mundigl O, Waldhauer I, Weinzierl T, Fauti T, et al. Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models. Mol Cancer Ther. 2013;12(10):2031–2042. doi: 10.1158/1535-7163.MCT-12-1182. - DOI - PubMed

Publication types

MeSH terms

Supplementary concepts

Associated data