The future development of bevacizumab in colorectal cancer

Bevacizumab (Avastin), the first approved therapy designed to inhibit tumor angiogenesis, has significant clinical benefits in the management of colorectal cancer (CRC). When bevacizumab is added to IFL (5-fluorouracil [5-FU]/leucovorin [LV]/irinotecan [Camptosar)]) as first-line therapy for metastatic CRC, significant overall and progression-free survival benefits are obtained. Similar survival benefits may be achieved when bevacizumab is added to 5-FU/LV alone. In addition, additive and synergistic effects with a range of chemotherapeutic agents illustrate that bevacizumab has considerable potential in combination with existing therapeutic options. Clinical data indicate that bevacizumab is the only agent in addition to chemotherapy that has demonstrated survival benefit in the first- and second-line settings. In addition, bevacizumab is expected to produce clinical benefit in the adjuvant setting: inhibition of vascular endothelial growth factor should prevent the angiogenic switch in micrometastases, which is a key factor in malignancy. The clinical program is examining the activity of bevacizumab in combination with the likely future standard of care in both the metastatic and adjuvant treatment settings. Phase III trials (NO16966C, CONcePT and TREE-2) are studying the benefit of combining bevacizumab with oxaliplatin (Eloxatin)-based regimens. Similarly, in the adjuvant setting, phase III trials are assessing the efficacy and tolerability of bevacizumab in combination with oxaliplatin-based chemotherapy (AVANT, NSABP C-08).