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

• Published in: Gynecologic oncology 2019-12, Vol.155 (3), p.406-412
• Main Authors: Lorusso, D., Ferrandina, G., Colombo, N., Pignata, S., Pietragalla, A., Sonetto, C., Pisano, C., Lapresa, M.T., Savarese, A., Tagliaferri, P., Lombardi, D., Cinieri, S., Breda, E., Sabatucci, I., Sabbatini, R., Conte, C., Cecere, S.C., Maltese, G., Scambia, G.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Bevacizumab - administration & dosage; Bevacizumab - adverse effects; Carboplatin - administration & dosage; Carboplatin - adverse effects; Chemotherapy; Endometrial cancer; Endometrial Neoplasms - drug therapy; Endometrial Neoplasms - pathology; Female; Humans; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Progression-Free Survival; Prospective Studies
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2019.10.013

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. 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). 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). 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. •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.