Breaking down the evidence for bevacizumab in advanced cervical cancer: past, present and future.

Despite the introduction of screening and, latterly, vaccination programs in the developed world, globally cervical cancer remains a significant health problem. For those diagnosed with advanced or recurrent disease even within resource rich communities, prognosis remains poor with an overall survival (OS) of just over 12 months. New therapeutic interventions are urgently required. Advances in our understanding of the mechanisms underlying tumor growth and the downstream effects of human papilloma virus (HPV) infection identified angiogenesis as a rational target for therapeutic intervention in cervical cancer. Anti-angiogenic agents showed promising activity in early phase clinical trials culminating in a randomized phase III study of the humanized monoclonal antibody to vascular endothelial growth factor (VEGF), bevacizumab, in combination with chemotherapy. This pivotal study, the Gynecologic Oncology Group protocol 240, met its primary endpoint demonstrating a significant improvement in OS. Bevacizumab became the first targeted agent to be granted regulatory approval by the United States Food and Drug Administration for use alongside chemotherapy in adults with persistent, recurrent or metastatic carcinoma of the cervix. This review outlines the rationale for targeting angiogenesis in cervical cancer focusing on the current indications for the use of bevacizumab in this disease and future directions.