A number of orally administered angiogenesis inhibitors are being investigated for advanced ovarian cancer. The first of these, sorafenib (Nexavar®), is in phase 2 clinical trials for ovarian cancer both as first-line therapy and maintenance therapy. In one study, 120 women with newly diagnosed advanced ovarian cancer will undergo surgery to remove as much of the tumor as possible, followed by chemotherapy alone or with sorafenib11. A second single-arm phase 2 study is evaluating the combination of sorafenib and low-dose bevacizumab in women with advanced ovarian cancer that has become resistant to prior treatment12.
Cediranib (Recentin™) is another oral angiogenesis inhibitor that has shown promise for ovarian cancer. This agent is now being evaluated in a randomized, placebo-controlled, multi-stage phase 3 trial called ICON-613. The final stage of this study intends to randomize 2,000 women with relapsed ovarian cancer to one of three treatment arms: 6 cycles of chemotherapy plus a daily placebo for up to 18 months (placebo arm); chemotherapy plus daily oral cediranib for 6 cycles followed by a placebo (concurrent therapy arm); or chemotherapy plus daily cediranib followed by maintenance cediranib for up to 18 months (concurrent and maintenance arm).
Other oral angiogenesis inhibitors being studied for advanced ovarian cancer include: BIBF 1120 (Vargatef™), pazopanib (Votrient™), and cabozantinib (XL 184). A randomized, placebo-controlled phase 3 trial of pazopanib as maintenance therapy following first-line chemotherapy for ovarian cancer is currently enrolling patients14. BIBF 1120 was studied as maintenance therapy in 84 women who had responded to their most recent chemotherapy regimen15. BIBF 1120-treated patients had a 32% reduction in the risk of disease progression at 36 weeks compared with women who received a placebo. A randomized phase 3 trial called LUME-Ovar-1 has been initiated to evaluate the whether adding BIBF 1120 to front-line chemotherapy can improve PFS in women with advanced ovarian cancer16.
Results from a phase 2 study of cabozantinib in 70 women advanced ovarian cancer were recently presented at the 2011 ASCO annual meeting17. There was evidence of anti-tumor activity in more than 70% of women who received this agent, including a number of partial responses (at least 50% tumor shrinkage) among women with cancer that was resistant to platinum chemotherapy. Although this was a small study, the signs of drug activity in these patients with advanced disease and few remaining treatment options were encouraging.
Oral Antiangiogenic Treatment
Last updated July 5, 2011