Bevacizumab (B) plus gemcitabine (G) in patient (pts) with advanced pancreatic cancer (PC): Updated results of a multi-center phase II trial

Abstract

4009 Background: Vascular endothelial growth factor (VEGF) and its receptors are overexpressed in PC. In preclinical models, anti-VEGF antibodies suppress PC growth and potentiate the activity of gemcitabine. High VEGF expression correlates with advanced stage and decreased survival in PC pts. These data suggest that anti-VEGF therapy may have utility in PC. Bevacizumab (Avastin) is a recombinant humanized monoclonal antibody to VEGF. Methods: We are conducting a phase II trial of BG in advanced PC pts at 8 centers. Eligible pts have no prior chemotherapy (except 5-FU as a radiosensitizer); PS 0–2; measurable disease; no tumor invasion of major vessels; no bleeding or thrombosis. G 1000 mg/m2 is given over 30 minutes days (D) 1, 8, 15 every 28 D. B 10 mg/kg is given D 1, 15 every 28D. CT scans are obtained every 2 cycles. Plasma VEGF levels are obtained pretreatment. 45 pts enrolled 11/01–12/03. Pt characteristics: male 47%; median age 61 (range 42–83); PS: 0/1/2: 62%/36%/2%; stage IV 100%; liver metastases 80%; prior radiation 18%. Results: 182 cycles of BG have been administered (median 3, range <1–11). 42 pts are currently evaluable for response in this ongoing trial (median follow-up 5.7 months). There are 9 confirmed partial responses (21% PR) lasting a median of 9.4 months. 19 pts (45%) had stable disease lasting a median of 5.4 months. Median time to progression is 5.8 months (95% CI: 4.8, 9.1). Median survival is 9.0 months (95% CI: 7.4, 12.4); 6-month survival is 74%. Grade ¾ toxicities (% pts): neutropenia 33%; leukopenia 30%; thrombocytopenia 7%; thrombosis 12%; bowel perforation 5%; hypertension, proteinuria, and headache 2% each. Grade 5 toxicities: 1 gastrointestinal bleed, 1 bowel perforation. Pretreatment plasma VEGF levels in 32 pts (range 0–586 pg/ml) showed no correlation with either response (Fisher's exact test p=1.00) or survival (Log rank test p=0.70). Conclusion: BG is active and well-tolerated in advanced PC. The median survival of 9.0 months and the 74% 6-month survival are encouraging. A randomized phase III trial of BG vs. G is in development in the Cancer and Leukemia Group B. Supported by NCI grant N01-CM-17102. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech; Lilly Oncology Genentech Lilly Oncology Lilly Oncology