Editors' ChoiceOvarian Cancer

Another Window of Opportunity

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Science Translational Medicine  18 Jan 2012:
Vol. 4, Issue 117, pp. 117ec9
DOI: 10.1126/scitranslmed.3003695

Antiangiogenic therapies are becoming mainstays of treatment for several tumor types. These drugs that inhibit blood vessel growth have now been approved for use in colorectal, lung, neuroendocrine, glioblastoma, and renal cell cancer. In two new studies, bevacizumab, a monoclonal antibody against vascular endothelial growth factor A (VEGF-A), shows strong signs of efficacy in ovarian cancer—perhaps leading to another approval. Both studies tested bevacizumab in combination with carboplatin and paclitaxel, the conventional drugs for frontline chemotherapyin this cancer. In an international study by Perren et al., a total of 1528 patients with epithelial ovarian cancer were randomized to either carboplatin plus paclitaxel or carboplatin plus paclitaxel plus bevacizumab. The patients treated with bevacizumab showed superior median progression free survival (PFS) of 24.1 months; patients receiving the chemotherapy alone had a PFS of 22.4 months (P = 0.04 log-rank test). A subset of patients with a high risk for tumor progression did especially well, with a PFS of 18.1 months compared with 14.5 months for high-risk patients receiving chemotherapy alone. Similarly, in the Berger et al. study, 1873 women with advanced ovarian cancer were randomized to one of three groups: chemotherapy (carboplatin plus paclitaxel) plus placebo for 22 cycles (3 weeks per cycle), chemotherapy for 22 cycles plus bevacizumab for cycles 2 to 6, and chemotherapy plus bevacizumab for the full 22 cycles. Addition of bevacizumab for all 22 cycles increased the median PFS by 4 months over that of the placebo control group.

Together, these studies demonstrate that antiangiogenic therapies such as bevacizumab can delay progression of ovarian cancer. This opens a window of opportunity for additional agents in this class, including inhibitors of angiopoietin and the VEGF receptor tyrosine kinase. The primary challenges may be the side effects seen with these agents: In both of the new studies, increased incidence of hypertension and proteinuria were seen, and, more serious, events such as gastrointestinal wall perforation occurred at higher rates. Finding the optimal therapeutic window to balance efficacy and adverse events will be key in the further development of these agents.

T. J. Perren et al., A phase 3 trial of bevacizumab in ovarian cancer. N. Engl. J. Med. 365, 2484–2496 (2011). [Abstract]

R. A. Burger et al., Incorporation of bevacizumab in the primary treatment of ovarian cancer. N. Engl. J. Med. 365, 2473–2483 (2011). [Abstract]

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