| General information |
| Database: | DB00715 |
| Objective: | Their aim was to assess the use of bevacizumab in combination with oxaliplatinbased chemotherapy in the adjuvant treatment of patients with resected stage III or highrisk stage II colon carcinoma. |
| Authors: | de Gramont A, et al |
| Title: | Bevacizumab plus oxaliplatinbased chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial. |
| Journal: | Lancet Oncol. |
| Year: | 2012 |
| PMID: | 23168362 |
| Trial Design |
| Clinical Trial Id: | NCT00112918 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | stage III or highrisk stage II colon carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Bevacizumab plus oxaliplatinbased chemotherapy as adjuvant treatment |
| Study Type: | a prospective, multicentre, randomised, parallel, threearm, phase III trial |
| Key Patients Feature: | formed consent before study participation.Eligible patients were 18 years or older with histologically confi rmed stage III or highrisk stage II coloncarcinoma (defined by the American Joint CancerCommittee/Union Internationale Contre le Cancer).Surgery with curative intent was done 4-8 weeks beforerandomisation. Key exclusion criteria included: evidenceof remaining tumour; carcinoembryonic antigen levelsof more than 1.5 times the upper normal limit aftersurgery; previous antiangiogenic treatment; major surgical procedure, open biopsy, or significant traumaticinjury less than 28 days before study treatment; andabnormal haematological, liver, or renal function. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | FOLFOX4 vs. FOLFOX4+bevacizumab followed by bevacizumab monotherapy vs. bevacizumab+ XELOX followed by bevacizumab monotherapy |
| Treatment Info: | patients were randomly assigned (1:1:1) to receive FOLFOX4 (oxaliplatin 85 mg/m(2), leucovorin 200 mg/m(2), and fluorouracil 400 mg/m(2) bolus plus 600 mg/m(2) 22h continuous infusion on day 1; leucovorin 200 mg/m(2) plus fluorouracil 400 mg/m(2) bolus plus 600 mg/m(2) 22h continuous infusion on day 2) every 2 weeks for 12 cycles; bevacizumab 5 mg/kg plus FOLFOX4 (every 2 weeks for 12 cycles) followed by bevacizumab monotherapy 7.5 mg/kg every 3 weeks (eight cycles over 24 weeks); or bevacizumab 7.5 mg/kg plus XELOX (oxaliplatin 130 mg/m(2) on day 1 every 2 weeks plus oral capecitabine 1000 mg/m(2) twice daily on days 115) every 3 weeks for eight cycles followed by bevacizumab monotherapy 7.5 mg/kg every 3 weeks (eight cycles over 24 weeks). |
| Primary End Point: | diseasefree survival |
| Secondary End Point: | NA |
| Patients Number: | 2867 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | 27.0 months (95% CI 21.4-32.2) in the FOLFOX4 group, 23.8 months (18.5-26.4) in the bevacizumab-FOLFOX4 group, and 22.4 months (19.0-29.0) in the bevacizumab-XELOX group. |
| Median PFS A vs. C: | bevacizumab-FOLFOX4 versus FOLFOX4 was 1.17 (95% CI 0.98-1.39; p=0.07), and for bevacizumab-XELOX versus FOLFOX4 was 1.07 (0.90-1.28; p=0.44). |
| Median OS A vs. C: | After a minimum followup of 60 months, the overall survival hazard ratio for bevacizumab- FOLFOX4 versus FOLFOX4 was 1.27 (1.03-1.57; p=0.02), and for bevacizumab-XELOX versus FOLFOX4 was 1.15 (0.93-1.42; p=0.21). |
| Adverse Event(agent arm): | The most common grade 3-5 adverse events were neutropenia (FOLFOX4: 477 [42%] of 1126 patients, bevacizumabFOLFOX4: 416 [36%] of 1145 patients, and bevacizumab-XELOX: 74 [7%] of 1135 patients), diarrhoea (110 [10%], 135 [12%], and 181 [16%], respectively), and hypertension (12 [1%], 122 [11%], and 116 [10%], respectively). Serious adverse events were more common in the bevacizumab groups (bevacizumab-FOLFOX4: 297 [26%]; bevacizumab-XELOX: 284 [25%]) than in the FOLFOX4 group (226 [20%]). Treatmentrelated deaths were reported in one patient receiving FOLFOX4, two receiving bevacizumab-FOLFOX4, and fi ve receiving bevacizumab-XELOX. |
| Conclusions: | Bevacizumab does not prolong diseasefree survival when added to adjuvant chemotherapy in resected stage III colon cancer. Overall survival data suggest a potential detrimental effect with bevacizumab plus oxaliplatinbased adjuvant therapy in these patients. On the basis of these and other data, they do not recommend the use of bevacizumab in the adjuvant treatment of patients with curatively resected stage III colon cancer. |