Highlights
- •Bevacizumab combined with chemotherapy does not increase PFS in comparison to chemotherapy in recurrent endometrial cancer.
- •Cardiovascular events were more frequent in the bevacizumab arm.
- •Secondary endpoint suggests activity of bevacizumab in endometrial cancer which merits further exploration.
Abstract
Objective
Increased Vascular Endothelial Growth Factor Receptor (VEGF) expression in endometrial
cancer (EC) is associated with a poor prognosis. Preliminary clinical data reported
Bevacizumab effectiveness in EC both as single agent and in combination with chemotherapy.
Methods
In a phase II trial, patients with advanced (FIGO stage III-IV) or recurrent EC were
randomized to receive Carboplatin-Paclitaxel standard dose for 6–8 cycles vs Carboplatin-Paclitaxel
and Bevacizumab 15 mg/kg in combination with chemotherapy and maintenance until disease
progression or unacceptable toxicity. The primary endpoint was progression free survival
(PFS).
Results
108 patients were randomized; PFS (10.5 vs 13.7 months, HR 0.84 p = 0.43), overall
response rate (ORR 53.1% vs 74.4%) and overall survival (OS) (29.7 vs 40.0 months,
HR 0.71 p = 0.24) resulted in a non-significant increase in Bevacizumab treated patients.
The PFS increase became significant when an exploratory analysis with the Breslow
test was used. Moreover, patients treated with Bevacizumab experienced a significant
increase in 6-month disease control rate (70.4% vs 90.7%). Cardiovascular events were
more frequent in the experimental arm (“de novo” grade ≥2 hypertension 21% vs 0% and
grade ≥2 thromboembolic events 11% vs 2% in the Bevacizumab vs standard treatment
arm, respectively).
Conclusions
Bevacizumab combined with chemotherapy in the treatment of advanced/recurrent EC failed
to demonstrate a significant increase in PFS in the MITO END-2 trial. Nevertheless,
these preliminary data suggests some effectiveness of the antiangiogenic agent which
merits further exploration in a larger population with a better molecular characterization.
Keywords
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Article info
Publication history
Published online: October 30, 2019
Accepted:
October 12,
2019
Received in revised form:
October 10,
2019
Received:
August 14,
2019
Identification
Copyright
© 2019 Elsevier Inc. All rights reserved.
