Bevacizumab (Avastin^®)
Bevacizumab (Avastin^®) has been evaluated in a number of clinical studies in advanced ovarian cancer. One of the largest phase 2 studies of bevacizumab for advanced ovarian cancer involved 62 women, most of whom had been previously treated with or were resistant to chemotherapy⁵. Bevacizumab was administered as a single agent at a relatively high dose. In this study, 21% of the women had their tumors either stop growing or shrink. The average duration of response was just over 10 months, which was considered a promising result given the women’s’ advanced stage of disease and the lack of remaining treatment options.

Two other recent phase 2 studies have evaluated bevacizumab in combination with chemotherapy. In the first, bevacizumab was administered with two standard chemotherapy drugs, carboplatin and paclitaxel, to 62 women with newly diagnosed advanced ovarian cancer⁶. Researchers reported that 76% of the women responded to the drug combination, and more than half had at least some shrinkage of their tumors. A second study paired bevacizumab with a newer formulation of paclitaxel called nab-paclitaxel (Abraxane^®) in 48 women with advanced ovarian cancer that was highly resistant to chemotherapy⁷. In this study, just under half of the women (46%) had partial tumor shrinkage.

Results have recently been reported from three phase 3 clinical trials of bevacizumab in advanced ovarian cancer. The first of these, GOG 0218, was a placebo-controlled study in 1,873 women with advanced ovarian cancer who had received no prior therapy⁸. The women were randomly assigned to receive either standard first-line chemotherapy (carboplatin and paclitaxel) plus bevacizumab, or chemotherapy plus a placebo. A third treatment arm continued bevacizumab as a single agent following its initial use with chemotherapy.

Results showed that women who got the bevacizumab-chemotherapy combination followed by single-agent bevacizumab lived about 4 months longer without their cancer getting worse—a measurement known as progression-free survival (PFS)—compared with those who got chemotherapy with a placebo. For women who received bevacizumab plus chemotherapy without continued bevacizumab, PFS was prolonged by about a month versus chemotherapy alone, but this improvement was not statistically significant, meaning that it could have occurred by chance.

The second phase 3 study, ICON-7, was a two-arm trial without a placebo group that enrolled more than 1,500 women with advanced ovarian cancer living in Australia and western Europe⁹. Women were randomly assigned to receive either standard chemotherapy or chemotherapy plus bevacizumab followed by single-agent bevacizumab. Preliminary data presented at a European oncology meeting last year showed that adding bevacizumab to chemotherapy improved PFS by 1.7 months over chemotherapy alone. Final survival results from ICON-7 are expected in early 2012.

Most recently, results from a phase 3 trial called OCEANS were announced at the 2011 American Society of Clinical Oncology (ASCO) annual meeting in Chicago. OCEANS is a randomized, placebo controlled study that compared the use bevacizumab with chemotherapy (gemcitabine and carboplatin) followed by bevacizumab alone versus chemotherapy alone¹⁰. They study enrolled 484 women with recurrent ovarian cancer who had received no more than one prior treatment regimen. Women who got bevacizumab had a 52% reduction in the risk of disease progression compared with women who only received chemotherapy. Median PFS improved from 8.4 months for women in the chemotherapy alone group to 12.4 months in the bevacizumab plus chemotherapy group.

Several other phase 3 clinical trials of bevacizumab for ovarian cancer are ongoing. These studies involve the use of bevacizumab with several chemotherapy drugs in differing doses and combinations.