D Lorusso1, G Ferrandina2, N Colombo3, S Pignata4, A Pietragalla5, C Sonetto6, C Pisano4, M T Lapresa7, A Savarese8, P Tagliaferri9, D Lombardi10, S Cinieri11, E Breda12, I Sabatucci6, R Sabbatini13, C Conte5, S C Cecere4, G Maltese6, G Scambia2. 1. Department of Woman, Child and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. Electronic address: domenica.lorusso@policlinicogemelli.it. 2. Department of Woman, Child and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Department of Woman, Child and Public Health, Catholic University of the Sacred Heart, Rome, Italy. 3. Gynecologic Oncology Program, IEO, European Institute of Oncology IRCCS, Milan, Italy; Department of medicine and surgery, University of Milan-Bicocca, Milan, Italy. 4. Department of Oncology, Fondazione Pascale National Cancer Institute, Naples, Italy. 5. Department of Woman, Child and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 6. Gynecologic Oncology Unit, Fondazione IRCCS National Cancer Institute, Milan, Italy. 7. Gynecologic Oncology Program, IEO, European Institute of Oncology IRCCS, Milan, Italy. 8. Department of Oncology, Regina Elena National Cancer Institute, Rome, Italy. 9. Department of Oncology, Magna Grecia University, Catanzaro, Italy. 10. Department of Oncology, CRO, Aviano, Italy. 11. Department of Oncology, Di Summa-Perrino Hospital, Brindisi, Italy. 12. Department of Oncology, Fatebenefratelli Hospital, Rome, Italy. 13. Department of Oncology, University of Modena and Reggio Emilia, Italy.
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.
RCT Entities:
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.
Authors: Kimberly K Leslie; Virginia L Filiaci; Adrianne R Mallen; Kristina W Thiel; Eric J Devor; Katherine Moxley; Debra Richardson; David Mutch; Angeles Alvarez Secord; Krishnansu S Tewari; Megan E McDonald; Cara Mathews; Casey Cosgrove; Summer Dewdney; Yovanni Casablanca; Amanda Jackson; Peter G Rose; XunClare Zhou; Michael McHale; Heather Lankes; Douglas A Levine; Carol Aghajanian Journal: Gynecol Oncol Date: 2021-02-02 Impact factor: 5.482
Authors: David S Miller; Virginia L Filiaci; Robert S Mannel; David E Cohn; Takashi Matsumoto; Krishnansu S Tewari; Paul DiSilvestro; Michael L Pearl; Peter A Argenta; Matthew A Powell; Susan L Zweizig; David P Warshal; Parviz Hanjani; Michael E Carney; Helen Huang; David Cella; Richard Zaino; Gini F Fleming Journal: J Clin Oncol Date: 2020-09-29 Impact factor: 44.544
Authors: Heidi Rütten; Cornelia Verhoef; Willem Jan van Weelden; Anke Smits; Joëlle Dhanis; Nelleke Ottevanger; Johanna M A Pijnenborg Journal: Cancers (Basel) Date: 2021-12-14 Impact factor: 6.639