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

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.

Role of conservative surgery in ovarian cancer: the European experience.

Although less frequently than in older women, about 15% of invasive epithelial ovarian cancer may occur in young women, for whom preservation of fertility potential is an important clinical goal. We reviewed the published evidences from the European literature on the role of conservative surgery in women with invasive epithelial ovarian cancer. Three reports were identified from the Italian and French literature; the data were analyzed together with our own experience in terms of relapse rate, relapse in the preserved ovary, survival, and fertility outcome. A total of 152 conservative surgeries were reported: 88 patients with stage IA, 2 with stage IB, 51 with stage IC, 2 with stage II, 3 with stage IIIA, and 6 with stage IIIC. Relapses occurred in 18/152 patients (11.8%) and involved the preserved ovary in 11 cases (7%). Fifty-three pregnancies were recorded with 38 uneventful term deliveries, 2 ectopic pregnancies, 6 spontaneous abortions, 4 terminations, and 2 with unknown outcome. Nine patients (5.9%) have died of disease. These findings confirm that young women with stage I invasive epithelial ovarian cancer may receive a successful treatment of their disease without sacrificing fertility.