ISY-14-5 - Antiangiogenic therapy in gynecologic malignancy

Abstract

Ovulation and corpus luteum formation is heavily regulated by vascular endothelial growth factor (VEGF), so the sensitivity of ovarian cancer to VEGF inhibitors is not surprising. Randomized trials with bevacizumab and tyrosine kinase inhibitors (TKIs) have validated VEGF as a target in this disease. Results of studies in first-line (GOG218, ICON7), second-line platinum-sensitive (OCEANS), and recurrent platinum-resistant (AURELLIA) settings have shown significant improvements in progression-free survival. Results of ICON7 in the advanced and high-risk first-line setting have shown an advantage in overall survival, whereas results of another trial in the platinum sensitive recurrent disease setting (ICON6) have shown improvement in overall survival, but it was not significant. Patients treated with a combination of the VEGFR TKI cediranib with the PARP inhibitor olaparib yielded striking improvements in progression-free survival and highlighted the possibility of treating ovarian cancer with orally bioavailable molecularly targeted therapy. Studies with an unlicensed angiopoietin inhibitor have identified improvements in progression-free survival (TRINOVA-1). As biomarker science matures, investigation of whether some ovarian cancers are sensitive to angiopoietin inhibitors and others to VEGF inhibitors, and whether resistance to one is determined by the other, will be interesting. However, antibodies that target both pathways are being developed. Uterine cervical cancer has been assessed for its sensitivity to VEGF inhibitors. Bevacizumab was approved on the basis of results of a randomized trial (GOG240) in recurrent or metastatic cervical cancer, in which 452 patients were randomly allocated to cytotoxic chemotherapy with or without bevacizumab. Treatment with bevacizumab improved overall survival from 13.3 months to 17 months and progression-free survival from 5.9 months to 8.2 months.