3989 - Bevacizumab as adjuvant treatment for colon cancer: Updated results from the AVANT phase III Study by the GERCOR Group

Background

The AVANT study, with a median follow-up (FU) of 4 years, did not improve disease-free survival (DFS; the primary endpoint) with the addition of bevacizumab to oxaliplatin-based chemotherapy in stage III resected colon cancer (de Gramont A, Lancet Oncol, 2012). We report here long-term results with 10-year maximum FU.

Methods

OS and DFS calculation was done by the Kaplan-Meier method and Cox regression model. Cause of death distribution was evaluated with the chi-square test.

Results

2867 patients had stage III colon cancer (arm A: FOLFOX4, n = 955; arm B: FOLFOX4-bevacizumab, n = 960; arm C: XELOX-bevacizumab, n = 952). With a median FU of 6.73 years (5.51-10.54), 672 patients died, of whom 198 (20.7%) in arm A, 250 (26.0%) in arm B, and 224 (23.5%) in arm C. The 3-year DFS rates were 76.9%, 73.7%, and 75.2% in arms A, B, and C, respectively and the 5-year OS rates were 84.7%, 80.8%, and 81.7%, (DFS P = 0.1743 and OS P = 0.0294). The OS hazard ratio was 1.29 (95% CI 1.07-1.55; P = 0.008) for arm B vs arm A and 1.15 (95% CI 0.95-1.39; P = 0.1474) for arm C vs arm A. The DFS hazard ratio was 1.16 (95% CI 0.99-1.37; P = 0.0626) for arm B vs arm A and 1.1 (95% CI 0.93-1.29; P = 0.2690) for arm C vs arm A. Colon cancer-related deaths occurred in 542 among 672 dead patients (80.7%); arm A: 157/198 (79.3%); arm B: 205/250 (82.0%), arm C:180/224 (80.4%), with no difference between arms (P = 0.7641). Non-colon cancer-related deaths occurred in 130 patients: arm A: 41 (20.7%); arm B: 45 (18.0%), arm C: 44 (19.6%). The 8-year OS rate in patients alive without relapse at 4 years was 95.2%, 94.7%, and 95.4% in arm A, B, and C respectively. Deaths related to cardiovascular diseases and sudden deaths were reported in 13 (6.6%), 17 (6.8%), and 14 (6.3%) patients, in arm A, B, and C respectively. In Cox analysis, gender, age, histological grade, performance status, and T and N stage were independent prognostic factors for DFS in stage III.

Conclusions

Updated result of the AVANT study is consistent with the primary reported data concerning DFS, with a potential detrimental effect of the addition of bevacizumab to oxaliplatin-based adjuvant therapy on OS, in patients with stage III colon cancer, without increase in non-colon cancer-related deaths.

Clinical trial identification

NCT00112918.

Editorial acknowledgement

Magdalena Benetkiewicz (GERCOR).

Legal entity responsible for the study

Hoffmann-La Roche.

Funding

Roche.

Disclosure

T. André: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD Oncology; Honoraria (self), Travel / Accommodation / Expenses: Roche/Ventana; Honoraria (self): Sanofi; Honoraria (self), Advisory / Consultancy: Servier; Honoraria (self): Chugai; Honoraria (self): Yakult; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: HalioDx. D. Vernerey: Advisory / Consultancy: HalioDx; Honoraria (self), Advisory / Consultancy: Janssen-Cilag; Advisory / Consultancy: OSE Immunotherapeutics; Advisory / Consultancy: Prestizia; Honoraria (self): Celgene. G.M. Bodoky: Advisory / Consultancy: Bayer; Advisory / Consultancy: Ipsen; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche. F. Rivera: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Merck Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Celgen; Advisory / Consultancy, Research grant / Funding (self): MSD; Honoraria (self): Tecnofarma. R. Geva: Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self): Lilly; Honoraria (self): Medison; Honoraria (self), Travel / Accommodation / Expenses: Roche; Honoraria (self): Janssen; Honoraria (self): Takeda; Honoraria (institution), Travel / Accommodation / Expenses: Merck; Travel / Accommodation / Expenses: GAD Medical; Research grant / Funding (institution), Educational grant to the research unit - Novartis: Novartis. P. Österlund: Honoraria (self), Research grant / Funding (institution), Travel /Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation /Expenses: Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Nordic Drugs; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Baxalta/Servier; Honoraria (self), Speaker Bureau / Expert testimony: Eisai; Travel / Accommodation / Expenses: AbbVie; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Pierre Fabre. E. Van Cutsem: Advisory / Consultancy, Research grant / Funding (self): Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Bayer; Honoraria (self): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Servier; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (self): Merck; Advisory / Consultancy, Research grant / Funding (self): MSD; Advisory / Consultancy, Research grant / Funding (self): Ipsen; Advisory / Consultancy, Research grant / Funding (self): Sanofi; Advisory / Consultancy, Research grant / Funding (self): Boehringer. D. Cunningham: Research grant / Funding (institution): Amgen; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Medimmune; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Merrimack; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Roche. J. Tabernero: Honoraria (self), Advisory / Consultancy: Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsenm Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Partn; Research grant / Funding (institution): Agendia BV, Amgen SA, Debiopharm International SA, Janssen-Cilag SA, Mologen AGm Novartis Farmacéutica SA, Pharma Mar, Roche Farma SA, Laboratorios Servier SL, Symphogen A/S; Honoraria (self), Leadership role: American Society of Clinical Oncology - ASCO. American Association for Cancer Research - AACR. European Organization for Research and Treatment of Cancer - EORTC. Cancer Core Europe (CCE). Worldwide Innovative Networking (WIN) Consortium in Personalized C; Leadership role, Non-remunerated activity/ies: Institute for Biomedical Research (IRB) Bellinzona (2013). IRCC Candiolo Cancer Institute (2013-2017). University Medical Centre Utrecht (UMC Utrecht) (2014). Cambridge Cancer Centre (2014). Institut Gustave Roussy (2015). German Consortium for Translation. A. De Gramont: Honoraria (self): Yakult; Honoraria (self): Chugai Pharma. All other authors have declared no conflicts of interest.