Dana Chase, MD
Three pivotal clinical trials have shown the significance of the angiogenesis inhibitor bevacizumab (Avastin) as treatment for patients with recurrent ovarian cancer. However, asks Dana Chase, MD, what else can be accomplished with this agent to provide a greater benefit to patients?
The randomized phase III GOG-02131
and OCEANS trials2
were the basis for the FDA’s December 2016 expanded approval of bevacizumab in ovarian cancer to include patients with platinum-sensitive recurrent disease as part of a combination regimen with chemotherapy followed by continued use of the angiogenesis inhibitor.
In GOG-0213, results demonstrated that the addition of bevacizumab to chemotherapy led to a nonstatistically significant median overall survival (OS) difference of 5 months versus chemotherapy alone of 42.6 months versus 37.3 months, respectively (HR, 0.84). The median progression-free survival (PFS) with bevacizumab was 13.8 months compared with 10.4 months with chemotherapy alone (HR, 0.61; 95% CI, 0.51-0.72).
The OCEANS study showed a median PFS improvement of 4 months for bevacizumab with chemotherapy (12.4 months) versus placebo plus chemotherapy (8.4 months; HR, 0.46; 95% CI, 0.37-0.58; P <.0001). However, the secondary endpoint of OS also did not show statistically significant improvement (HR, 0.95).
Moreover, the phase III AURELIA trial3
led to the November 2014 FDA approval of bevacizumab in combination with chemotherapy for patients with platinum-resistant recurrent ovarian cancer. The decision was based on a 62% improvement in PFS with bevacizumab demonstrated in the trial.
During the 2017 OncLive®
State of the Science Summit on Advanced Ovarian Cancer, Chase, an associate professor at Creighton University, University of Arizona College of Medicine, and gynecologist oncologist with Arizona Oncology, lectured on the use of bevacizumab in patients with recurrent disease. In an interview, she expanded on the pivotal clinical trials, managing toxicities with these regimens, and the questions researchers still need to answer regarding bevacizumab.
OncLive: Can you give an overview of your presentation on chemotherapy and bevacizumab regimens in ovarian cancer?
: Talking about recurrent ovarian cancer is one of the most challenging parts of being a gynecologic oncologist. These women had treatment before, they have had surgery, and now they’re suffering a recurrence. The approach to treatment for them can be very difficult. You are not only trying to manage a tumor that’s not resectable, but you’re also trying to manage toxicities. These women, at this point, know that they are not going to be cured. They have things they want to do in their life, and they don’t want to feel too sick. They are sick of feeling sick. You have to really manage disease control with toxicity, which is really important to consider in this patient population.
I talked about 3 trials: GOG-213, OCEANS, and AURELIA. Those 3 studies specifically led to the approval for bevacizumab, an antiangiogenesis therapy in recurrent ovarian cancer.
AURELIA is a study that looked at platinum-resistant patients with a doublet treatment, which includes a chemotherapy backbone with bevacizumab added to it. That study did show an improvement in PFS, and was very noteworthy for the improvement in quality of life and the reduction of abdominal symptoms. And, bevacizumab is a relatively easy-to-tolerate medication, so these patients really did not have much more toxicity.
GOG-0213 and OCEANS are both studies that led to the approval of bevacizumab in recurrent platinum-sensitive ovarian cancer. GOG-0213 used carboplatin with paclitaxel and bevacizumab, and the OCEANS study used carboplatin with gemcitabine and bevacizumab. GOG-0213 had an impressive improvement in OS and the OCEANS study had an improvement in PFS. Therefore, we are now allowed to treat platinum-sensitive patients with chemotherapy plus bevacizumab followed by bevacizumab maintenance. Again, the toxicity of bevacizumab maintenance is very easy to address in these patients; they are essentially able to get back to their normal lives.
Honing in on the toxicity profiles of some of these regimens, what advice do you have for managing side effects?
That is one of the most challenging parts of my job—managing these side effects. For example, with paclitaxel—one of the most commonly used drugs for ovarian cancer—I always tell my patients that the number 1 side effect that patients complain about is hair loss. Paclitaxel causes alopecia.