Findings from the AVANT trial do not support the use of bevacizumab in patients receiving oxaliplatin-based chemotherapy for resected stage III or high-risk stage II colon carcinoma.
Indeed, the results, published in The Lancet Oncology, indicate that patients treated with the vascular endothelial growth factor inhibitor did not achieve greater disease-free survival (DFS) than controls, and experienced more relapses and deaths due to progression.
"Consequently, bevacizumab should not be used in the adjuvant treatment of patients with curatively resected stage III colon cancer," say Aimery de Gramont (Hôpital Saint Antoine, Paris, France) and co-authors.
The phase III open-label trial randomly assigned stage III patients from 34 countries to receive 12 cycles of the FOLFOX4 regimen (oxaliplatin, leucovorin, and fluorouracil) alone, or alongside bevacizumab 5 mg/kg followed by eight cycles of bevacizumab 7.5 mg/kg for 3 weeks. A third group was treated with the XELOX regimen (oxaliplatin, capecitabine) for eight cycles followed by eight cycles of bevacizumab monotherapy 7.5 mg/kg for 3 weeks.
After a median of 48 months, intention-to-treat analysis showed that 25% of FOLFOX4 patients (n=955) had experienced relapse, a new cancer, or died, compared with 29% of bevacizumab-FOLFOX4 patients (n=960) and 27% of bevacizumab-XELOX patients (n=952).
The DFS ratios for bevacizumab-FOLFOX4 and bevacizumab-XELOX patients versus FOXFOX4 patients were 1.17 and 1.07, respectively. And the overall survival hazard ratios after a minimum of 60 months for bevacizumab-FOLFOX4 and bevacizumab-XELOX patients versus FOLFOX4 patients were 1.27 and 1.15, respectively.
When including safety data from a further 573 patients with high-risk stage II cancer, the researchers found the most common grade 3 to 5 adverse events were neutropenia, diarrhea, and hypertension.
Moreover, serious adverse events were significantly more common in the bevacizumab-FOXFOX4 and bevacizumab-XELOX patients than FOLFOX4 patients (26 and 25 vs 20%).Treatment-related deaths were reported for one FOLFOX4 patient, two bevacizumab-FOLFOX4, and five bevacizumab-XELOX patients.
"Although AVANT was adequately powered to answer the question of whether bevacizumab in combination with adjuvant chemotherapy significantly prolongs DFS in patients with stage III colon cancer, the results are not generalisable outside the adjuvant treatment of colon cancer," note de Gramont et al.
"An active research programme is continuing with bevacizumab as adjuvant therapy for other tumour types."
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