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

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 journalArticlepeer-review

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. © 2019 Elsevier Inc.
Original languageEnglish
Pages (from-to)406-412
Number of pages7
JournalGynecol. Oncol.
Volume155
Issue number3
DOIs
Publication statusPublished - 2019

Keywords

  • Bevacizumab
  • Chemotherapy
  • Endometrial cancer
  • bevacizumab
  • carboplatin
  • paclitaxel
  • antineoplastic agent
  • adult
  • advanced cancer
  • aged
  • anemia
  • arterial thromboembolism
  • Article
  • asthenia
  • bleeding
  • cancer combination chemotherapy
  • cancer control
  • cancer growth
  • cancer recurrence
  • comorbidity
  • comparative study
  • confusion
  • controlled study
  • drug efficacy
  • dyspnea
  • endometrium cancer
  • febrile neutropenia
  • female
  • fistula
  • heart arrhythmia
  • heart muscle ischemia
  • human
  • hypertension
  • leukopenia
  • maintenance chemotherapy
  • major clinical study
  • multicenter study
  • multiple cycle treatment
  • nausea
  • nephrotoxicity
  • neutropenia
  • open study
  • overall survival
  • patient compliance
  • phase 2 clinical trial
  • priority journal
  • progression free survival
  • randomized controlled trial
  • thrombocytopenia
  • thromboembolism
  • venous thromboembolism
  • clinical trial
  • endometrium tumor
  • middle aged
  • pathology
  • prospective study
  • tumor recurrence
  • very elderly
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols
  • Carboplatin
  • Endometrial Neoplasms
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Paclitaxel
  • Progression-Free Survival
  • Prospective Studies

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