Editor’s Note:
Two phase 3 trials published in the New England Journal of Medicine on December 29, 2011, found bevacizumab to be active as first-line therapy in advanced ovarian cancer. Although both trials showed an increase in progression-free survival [PFS], not enough time has elapsed to determine whether the drug extends overall survival. Furthermore, it is unclear whether bevacizumab in ovarian cancer is best used as first-line or second-line therapy. Recently, Drs. Robert Burger and Kenneth Swenerton participated in a Medscape virtual debate via email to address this question: "Should bevacizumab be used as first-line therapy in patients with advanced ovarian cancer?" Dr. Maurie Markman served as moderator. What follows is their conversation.
Evidence for First-Line Therapy
Maurie Markman, MD. Bob, you were lead author on one of the positive studies on bevacizumab in ovarian cancer patients. Could you please summarize the results of the 2 studies looking at front-line use of bevacizumab in ovarian cancer and give your interpretation of how the data should influence clinical practice?
Robert A. Burger, MD. We now have 3 positive phase 3 ovarian cancer trials for bevacizumab, 2 of them in the front-line setting -- GOG-0218 and ICON7. Both trials used PFS as a primary endpoint. The placebo-controlled, double-blind GOG trial, which enrolled only women with stage III incompletely resectable or stage IV disease, showed a 28% prolongation in PFS when bevacizumab was combined with standard chemotherapy and then extended up to a maximum of 16 additional cycles (about 10 months). There was no clinically significant detriment to quality of life in the bevacizumab cohort, and compared with the control group, the rate of treatment discontinuation due to adverse effects in the maintenance bevacizumab group was quite small.
For ICON7, in which the maximum number of postchemotherapy treatment cycles was 12 (about 7 months), there was also a statistically significant, though less pronounced, improvement in PFS. However, this trial involved a population at lower risk for progression over time, because it included patients with either high-risk early-stage disease or completely resected stage III disease. An exploratory analysis of PFS in the 465 patients enrolled to ICON7 who had stage III suboptimal or stage IV disease showed a statistically significant 32% improvement in PFS. Such an improvement is clinically important, particularly since the majority of patients with advanced, incompletely resected disease are at high risk for early progression and death from disease. The benefit to bevacizumab appears to be related mostly to duration of treatment. A limitation to the design of the front-line trials was discontinuation of bevacizumab after a predefined number of treatment cycles.
In the phase 3 OCEANS trial, which enrolled patients with platinum-sensitive recurrent disease at first relapse, PFS was improved by 52% when bevacizumab was continued until disease progression.