ASCO
2010 Annual Meeting
CHICAGO — The addition of bevacizumab as maintenance therapy to
first-line treatment with standard chemotherapy plus bevacizumab extended PFS
by 4 months in women with
advanced epithelial ovarian, primary peritoneal or fallopian
tube cancer.
Robert A. Burger, MD, director of the Women’s Cancer Center
at Fox Chase Cancer Center, said that the addition of bevacizumab (Avastin,
Genentech) reduced the risk for progression by 28%.
“Bevacizumab is the first molecular targeted and the first
antiangiogenic agent to demonstrate benefit in this population,” Burger
said. “Bevacizumab in combination with chemotherapy followed by
continuation of bevacizumab alone should be considered as one standard option
for women with this disease.”
Burger discussed results from the phase 3 GOG-0218 trial during a press
conference at the
2010 ASCO
Annual Meeting.
Researchers recruited 1,873 women with newly diagnosed stage III/IV
ovarian, primary peritoneal or fallopian tube cancer at centers in the United
States, Canada, South Korea and Japan. All patients in the study had undergone
debulking surgery.
Patients were assigned standard chemotherapy with paclitaxel and
carboplatin plus placebo maintenance (n=601), standard chemotherapy with
bevacizumab plus placebo maintenance (n=607) or standard chemotherapy with
bevacizumab followed by bevacizumab maintenance (n=609).
Burger said that after 17.4 months of follow-up, PFS in the chemotherapy
group alone was 10.3 months compared with 14.1 months for the group assigned
bevacizumab as maintenance therapy (HR=0.717). PFS was 11.2 months in the group
assigned chemotherapy with concurrent bevacizumab, but Burger said the
difference was not statistically significant.
Burger said the type and severity of adverse events were in line with
those typically associated with bevacizumab in combination with chemotherapy.
Patients in the bevacizumab maintenance group experienced slightly more grade-3
proteinuria (1.6% vs. 0.7% in both the other treatment arms). In both the
concurrent bevacizumab arm and the maintenance bevacizumab arm, 63.3% of
patients experienced grade 4 or greater neutropenia vs. 57.7% of patients in
the chemotherapy alone arm.
Subgroup data
Burger told HemOnc Today that subgroup analysis showed that no
patient characteristic conferred an advantage.
“When we looked at factors like age, stage and tumor debulking
level, and performance status, and we found the same relationship,” he
said. “We didn’t find any group that seemed to benefit more or
less.”
He added that researchers are doing more exploration into the genetic
profile of patients and their tumors to identify those who will enjoy a greater
benefit from bevacizumab.
“That’s going to be incredibly important in terms of the
personalized medicine approach we hope to gain as we refine our dataset,”
he said.
Burger said OS data is extremely immature — 1-year OS for all
groups is more than 90%, and there is no statistically significant difference
between the groups. He added that, because bevacizumab is widely available,
researchers cannot control for postrecurrence use; therefore, there may be a
confounding crossover effect that could make it difficult to observe a survival
benefit, if one exists.
“The reason the primary endpoint was PFS was because of a consensus
among the world’s experts on ovarian cancer published in 2005 by Annals
of Oncology that PFS was perhaps a more meaningful primary endpoint in
phase 3 ovarian cancer studies,” he said. “We can’t control for
the median of seven regimens that these patients receive throughout the course
of their disease history, and when there is a potential for crossover,
it’s a major issue.” – by Jason Harris
It is a question of cost of the drug vs. benefit conferred - there is no evidence of improvement in survival. There is no question this study was well done. There is no question bevacizumab improved time to progression. Both are important, but should the drug be used in clinical practice? That's something to be discussed by patients and providers. The alternative is to reserve the drug until progression, if there is progression. There are a number of questions remaining, especially considering the cost of the drug.
- Maurie Markman, MD
HemOnc Today Editorial Board member
Bevacizumab with chemotherapy plus maintenance bevacizumab offers us a
new potential treatment paradigm for women with stage III and stage IV ovarian
cancer. The goal of extending life without progression is that we hope that
symptoms will stay minimal and quality of life will be enhanced. Of course, it
will come down to a discussion between patients and providers about whether
they want to incorporate this treatment, but it is a very reasonable option for
women with this very difficult to treat disease.
– Jennifer C. Obel, MD
Attending
Physician, Northshore University Health System
For more information:
- Burger RA. #LBA001. Presented at: the 2010 ASCO Annual Meeting;
June 4-8; Chicago.
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