Bevacizumab (Vascular Endothelial Growth Factor Inhibitor)

Bevacizumab is a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF). The inhibition of VEGF prevents the angiogenic switch in micrometastases, which is a key factor in malignancy. Bevacizumab has also been shown to have inhibitory effects on VEGF receptor activation and vascular permeability, and induces apoptosis in tumour cells.¹

Colorectal cancer (CRC)

It is licensed for treating metastatic colorectal cancer with combinations either of fluorouracil and folinic acid, or of fluorouracil, folinic acid, and irinotecan. Bevacizumab is given by intravenous infusion.

• Bevacizumab (Avastin®), is the first approved therapy designed to inhibit tumour angiogenesis
• It has significant clinical benefits in the management of colorectal cancer.
• When bevacizumab is added to IFL (irinotecan / fluorocil / leucovorin)(Camptosar™) as first-line therapy for metastatic CRC, significant benefits are obtained.² People live on average 5 months longer with this treatment.
• Similar survival benefits may be achieved when bevacizumab is added to 5-FU/ leucovorin alone.
• Clinical data show that bevacizumab is the only agent in addition to chemotherapy that has demonstrated survival benefit in the first and second-line settings.
• Further trials e.g. QUASAR 2,³ will define its role in adjuvant therapy.

NICE are currently appraising the role of Bevacizumab in carcinoma of the colon. This is due for publication in November 2006.⁴

Breast cancer

Bevacizumab is also used as first-line chemotherapy in patients with recurrent breast cancer, in combination with paclitaxel.⁵ The addition of bevacizumab to standard chemotherapy improves progression-free survival in breast cancer patients.⁶

Lung cancer

Last, but not least among the big killers, after breast cancer and colorectal cancer, non-small cell lung cancer (NSCLC) can now benefit from the addition of bevacizumab to standard first-line chemotherapy.

• Bevacizumab, in combination with carboplatin and paclitaxel, improved overall response and time to progression, in patients with advanced or recurrent non-small-cell lung cancer.
• Patients with nonsquamous cell histology appear to be a subpopulation with improved outcome and acceptable safety risks.⁷
• Careful patient selection is mandatory to avoid fatal bleeding following bevacizumab administration.⁸

Other metastatic disease

Bevacizumab also offers the potential to increase survival without substantially altering the toxicity profile in other tumour types.

• Bevacizumab has shown activity in patients with refractory metastatic renal cell carcinoma. Progression-free survival (PFS) was significantly longer in patients treated with bevacizumab (10 mg/kg every 2 weeks) than those treated with placebo. In addition, combining bevacizumab with erlotinib (Tarceva) has shown a median time to progression of more than 11 months.⁹
• Pancreatic cancer and other tumour types may also benefit when used first line in combination with standard therapy.