Phase II Study of Bevacizumab in Patients With Platinum-Resistant Ovarian Cancer or Peritoneal Serous Cancer

• Published in: Journal of clinical oncology Vol. 25; no. 33; pp. 5180 - 5186
• Main Authors: Cannistra, Stephen A., Matulonis, Ursula A., Penson, Richard T., Hambleton, Julie, Dupont, Jakob, Mackey, Howard, Douglas, Jeffrey, Burger, Robert A., Armstrong, Deborah, Wenham, Robert, McGuire, William
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 20.11.2007; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors - therapeutic use; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Bevacizumab; Biological and medical sciences; Drug Resistance, Neoplasm; Female; Humans; Intestinal Perforation - drug therapy; Intestinal Perforation - etiology; Intestinal Perforation - mortality; Medical sciences; Middle Aged; Neoplasms, Glandular and Epithelial - drug therapy; Neoplasms, Glandular and Epithelial - mortality; Organoplatinum Compounds - therapeutic use; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - mortality; Peritoneal Neoplasms - drug therapy; Peritoneal Neoplasms - mortality; Tumors; Human; Ovary cancer; Monoclonal antibody; Malignant tumor; Female genital diseases; Bevacizumab; Resistance; Ovarian diseases; Cancerology; Vascular endothelium growth factor; Treatment; Platinum; Phase II trial; Antagonist; Cancer; Peritoneum
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.2007.12.0782

We evaluated the efficacy and safety of bevacizumab in patients with platinum-resistant epithelial ovarian carcinoma (EOC) or peritoneal serous carcinoma (PSC) who had experienced disease progression during, or within 3 months of discontinuing, topotecan or liposomal doxorubicin. No more than three prior treatment regimens were allowed. Patients received single-agent bevacizumab 15 mg/kg intravenously every 3 weeks. Response was assessed by computed tomography (CT) scan every 6 weeks using Response Evaluation Criteria in Solid Tumors (RECIST). Of 44 patients treated, 83.7% were primarily platinum resistant, 59.1% had received liposomal doxorubicin, 25% topotecan, 15.9% both agents, and 47.7% had received three prior chemotherapy regimens. A median of five (range, two to 16) bevacizumab doses were administered. Partial responses were observed in seven patients (15.9%). Median progression-free survival was 4.4 months (95% CI, 3.1 to 5.5 months), with a median survival duration of 10.7 months at study termination. Bevacizumab-associated grade 3 to 4 events included hypertension (9.1%), proteinuria (15.9%), bleeding (2.3%), and wound-healing complications (2.3%). The incidence of GI perforation (GIP; 11.4%) was higher than reported in bevacizumab trials of other tumor types. GIP occurred in 23.8% of patients receiving three prior chemotherapy regimens, compared with 0% of patients receiving two prior chemotherapy regimens (P < .01). A trend toward higher risk of GIP was observed for patients with bowel wall thickening or bowel obstruction on CT scan. Arterial thromboembolic events occurred in three patients (6.8%). Three deaths were related to bevacizumab treatment. Bevacizumab has single-agent activity in patients with platinum-resistant EOC or PSC. A higher than expected incidence of GIP was noted in these heavily pretreated patients.