Avastin in Ovarian Cancer: Positive Results

Well, now that the American Society of Clinical Oncologists (ASCO) has met, we can review the data from GOG 218, the three-arm randomized trial that evaluated the role of bevacizumab (aka, Avastin) in the first-line treatment of ovarian cancer. To recall, back in February Genentech-Roche announced they had positive results from this trial though back then the data was not available for public scrutiny. The data has now been presented at ASCO by Dr. Robert Burger of Fox Chase Cancer Center, who presented the data on behalf of the Gynecologic Oncology Group (GOG), the National Cancer Institute sponsored cooperative group devoted to trials in gynecologic malignancies. [As a disclaimer, my institution and I personally are active members of the GOG and helped recruit women to this very large trial].

This trial enrolled almost 1900 women with advanced ovarian cancer (Stage III or IV) into one of 3 arms:

Arm I got Carboplatin and Paclitaxel (CP) chemotherapy followed by placebo maintenance (without more chemotherapy) for one year.

Arm II got CP and concurrent bevacizumab (Av) followed by placebo maintenance (without more chemotherapy) for one year.

Arm III got CP-Av followed by Av maintenance (without more chemotherapy) for one year.

In terms of having your disease not gete worse (aka Progression-Free survival [PFS]) women in Arm I went 10.3 months while those in Arm II went 11.2 months, which is not very dramatic. However, women in Arm III went 14.1 months, which was a 30% improvement in PFS, and this was statistically signficant. The cost of this gain was a greater risk of significant hypertension which developed in 10% of women on Arm III, versus 1.6% in Arm I and 5.4% in Arm II. The risk of perforating the GI tract was less than 3% in all arms. It was far too early to report on overall survival, unfortunately, to make any informed conclusions.

What to make of this data? I think one of the first questions one must ask is whether or not someone presenting with advanced ovarian cancer can be cured? If the answer is yes, then is PFS a good enough endpoint? If the answer is no, then is PFS a good enough endpoint?! That women presenting with advanced ovarian cancer can be cured is likely not realistic. We know that with our best treatments, 70% will relapse and most within three years. So gains in PFS should be strongly considered, particularly because halting a disease from getting worse will likely translate into a benefit in quality of life. Yet, even that is dependent on more than just survival-- it is dependent on the symptoms experienced while she is surviving that matters in terms of quality of life.

So in the end, PFS, while an exciting statistical endpoint, requires much more information to judge its impact. We need to place it in context in terms of Quality of Life and also in terms of the benefits in overall survival experienced.

Bevacizumab is an important agent in ovarian cancer and this has been shown in women with recurrent disease in several important studies. This data suggests yet another important strategy for treatment, but is it the best? My impression is that it solidifies my belief that women with ovarian cancer (including peritoneal and fallopian tube cancers) should have an opportunity for treatment with bevacizumab. Where the most appropriate place is to use it remains an active question important enough to keep asking.

For more information:

R. A. Burger, M. F. Brady, M. A. Bookman, J. L. Walker, H. D. Homesley, J. Fowler, B. J. Monk, B. E. Greer, M. Boente, S. X. Liang. Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study. J Clin Oncol 28:7s, 2010 (suppl; abstr LBA1). Available at: http://abstract.asco.org/AbstView_74_52788.html.