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
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
  • Bevacizumab/administration & dosage/adverse effects
  • Carboplatin/administration & dosage/adverse effects
  • Endometrial Neoplasms/*drug therapy/pathology
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local/drug therapy/pathology
  • Paclitaxel/administration & dosage/adverse effects
  • Progression-Free Survival
  • Prospective Studies

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