2735 - Bevacizumab plus Oxaliplatin-Based Chemotherapy as Adjuvant Treatment for Colon Cancer (CC): Updated analysis of stage II disease from the AVANT Phase III Randomized trial by the GERCOR Group

Background

The AVANT study did not demonstrate disease-free survival (DFS) benefit of the addition of bevacizumab to oxaliplatin-based chemotherapy in stage III resected CC and suggested a potential detrimental effect on overall survival (OS) (A. de Gramont et al. Lancet Oncol. 2012). Here, we present the results of the AVANT study for stage II CC patients.

Methods

The primary endpoint of AVANT was DFS for stage III disease. As an exploratory measure, AVANT also included high-risk stage II CC defined by T4, bowel obstruction or perforation, blood and/or lymphatic vascular invasion and/or perineural invasion, age <50 years, less than 12 nodes analyzed. OS and DFS were estimated by the Kaplan Meier method and compared by log-rank test and Cox regression model.

Results

573 patients had stage II CC (arm A: FOLFOX4, n = 192; arm B: FOLFOX4-bevacizumab, n = 194; arm C: XELOX-bevacizumab, n = 187), of whom 38 (19.8%) in arm A, 36 (18.6%) in arm B, and 40 (21.4%) in arm C had relapsed, developed a new CC, or died after a median follow-up of 6.86 years (IQR: 6.13-11.34). The DFS hazard-ratio was 0.94 (95% CI 0.59-1.48; P = 0.78) for arm B vs arm A and 1.07 (95% CI 0.69-1.67; P = 0.76) for arm C vs arm A. The OS hazard ratio was 0.92 (95% CI 0.55-1.55; P = 0.76) for arm B vs arm A and 0.85 (95% CI 0·50-1.44; P = 0.55) for arm C vs arm A. Safety data of stage II and stage III CC have been reported previously. In multivariable analysis, T4 vs T3-1 (P = 0.041), number of examined nodes (P = 0.005), and age (P = 0.0008) were prognostic for DFS. The 3-year DFS and 5-year OS rates of stage II were 88.2% (95% CI 83.7%-93.0%) and 89.7% (95% CI 85.4%-94.2%) in arm A, 86.6% (95% CI 81.8%-91.6%) and 89.7% (95% CI 85.4%-94.2%) in arm B, 86.7% (95% CI 81.8%-91.8%) and 93.2% (95% CI 89.6%-97.0%) in arm C, respectively.

Conclusions

In this exploratory analysis, bevacizumab did not prolong DFS and OS when added to adjuvant oxaliplatin-based chemotherapy in resected high-risk stage II patients with CC.

Clinical trial identification

NCT00112918.

Editorial acknowledgement

Magdalena Benetkiewicz (GERCOR).

Legal entity responsible for the study

GERCOR.

Funding

Roche.

Disclosure

A. De Gramont: Honoraria (self): Yakult; Honoraria (self): Chugai Pharma. T.W. Kim: Research grant / Funding (self): Merck Serono; Research grant / Funding (self): Pfizer; Research grant / Funding (self): AstraZeneca. J. Gallego-Plazas: Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy: Roche; Advisory / Consultancy: Bayer; Advisory / Consultancy: Lilly; Advisory / Consultancy: Celgene; Advisory / Consultancy: Merck; Travel / Accommodation / Expenses: Novartis; Leadership role, Study Coordinator of Agamenon study in advanced gastric cancer: Agamenon study. A. Cervantes: Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution): Servier; Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Takeda; Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Research grant / Funding (institution): Roche Beigene; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: Foundation Medicine; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Fibrogen; Research grant / Funding (institution): Amcure; Research grant / Funding (institution): Sierra Oncology; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Medimmune; Research grant / Funding (institution): BMS; Research grant / Funding (institution): MSD; Leadership role, Executive Board member of ESMO: not remunerated Chair of Education of ESMO: not remunerated General and Scientific Director of INCLIVA: not remunerated Associate Editor of ESMO Open: not remunerated Associate Editor of Annals of Oncology: remunerated Editor in Chief of Cancer Treatment Reviews: remunerated: Executive Board member of ESMO: not remunerated Chair of Education of ESMO: not remunerated General and Scientific Director of INCLIVA: not remunerated Associate Editor of ESMO Open: not remunerated Associate Editor of Annals of Oncology: remunerated. D.J. Jonker: Research grant / Funding (institution): Hoffman-La Roche; Non-remunerated activity/ies, Chair of the GI Disease Site Committee of the Canadian Cancer Trials Group: Canadian Cancer Trials Group. A. Dewdney: Honoraria (self), Chairing evening meetings: Servier; Honoraria (self): Roche. T. (Sirisingha) Dejthevaporn: Honoraria (self): Roche; Honoraria (self): Eisai; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): Eli Lilly; Leadership role: Thai Society of Clinical Oncology (TSCO). M. Moehler: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche. 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), Advisory / Consultancy, 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. All other authors have declared no conflicts of interest.