Carboplatin-paclitaxel compared to Carboplatin-Paclitaxel-Bevacizumab in advanced or recurrent endometrial cancer: MITO END-2 - A randomized phase II trial

D. Lorusso, G. Ferrandina, N. Colombo, S. Pignata, A. Pietragalla, C. Sonetto, C. Pisano, M. T. Lapresa, A. Savarese, P. Tagliaferri, D. Lombardi, S. Cinieri, E. Breda, I. Sabatucci, R. Sabbatini, C. Conte, S. C. Cecere, G. Maltese, G. Scambia

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)406-412
Number of pages7
JournalGynecologic Oncology
Volume155
Issue number3
DOIs
Publication statusPublished - Dec 2019

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Keywords

  • Bevacizumab
  • Chemotherapy
  • Endometrial cancer

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology

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