No overall survival benefit for bevacizumab in ovarian cancer
medwireNews: Addition of bevacizumab to first-line platinum-based chemotherapy does not improve overall survival in women with ovarian cancer, according to the mature data of the ICON7 trial.
But a subgroup of patients at high risk of disease progression could benefit from receiving the vascular endothelial growth factor (VEGF) inhibitor, report Adrian Cook (University College London, UK) and team in The Lancet Oncology.
In the phase III ICON7 trial, women with newly diagnosed epithelial ovarian, fallopian tube or primary peritoneal cancer were randomly assigned to receive carboplatin and paclitaxel either with or without bevacizumab.
The treatment arms were comparable with respect to survival, with a restricted mean survival of 45.5 months for the 764 participants who received bevacizumab and 44.6 months for the 764 who did not, where the restricted mean survival was the area under the survival curve for up to 5 years.
But in patients with stage IV disease or inoperable or suboptimally debulked stage III disease, the addition of bevacizumab resulted in a significant improvement in restricted mean survival, at 39.3 months for the 248 women given bevacizumab plus chemotherapy and 34.5 months for the 254 treated with chemotherapy alone.
And the favourable effect of bevacizumab increased with worsening disease prognosis, with hazard ratios for survival of 0.95, 0.84, 0.76 and 0.52 for stage III tumours between 0 and 1 cm, stage III tumours larger than 1 cm, stage IV disease, and inoperable disease, respectively.
The survival benefit bestowed by bevacizumab did not extend to non-high-risk participants or other subgroups with poor prognosis, such as patients with clear cell tumours and those with low-grade serous malignancies.
“These observations provide a clinical framework for the appropriate use of bevacizumab in ovarian cancer that is consistent with the biological requirement for angiogenesis in growing tumours, and a hypothetical framework to explain this effect biologically”, say the researchers.
“Our data suggest that a residual physical tumour burden, presumably producing VEGF, is necessary to enable bevacizumab to exert its effect on the tumour microenvironment.”
In a linked commentary, Joyce Liu and Ursula Matulonis, both from Dana-Farber Cancer Institute in Boston, Massachusetts, USA, write that despite the “tantalising possibility that a patient subgroup might derive an overall survival benefit from first-line bevacizumab, caution should be exercised when interpreting subset analyses”.
They conclude: “Additional studies to understand the effect of subsequent bevacizumab treatment on survival and to further identify and validate molecular markers of anti-angiogenic response will be important to better define our understanding of the role of bevacizumab therapy in ovarian cancer.”
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