Improved progression free survival (PFS), and rapid, sustained decrease in tumor perfusion among patients with advanced carcinoid treated with bevacizumab

Abstract

4007 Background: Carcinoid is a vascular tumor that expresses VEGF. Effective systemic therapy for advanced disease is lacking. We are evaluating anti-angiogenic therapy in a phase II study of Bevacizumab (BVZ) and PEG Interferon alpha-2b (PEGI) in patients with metastatic or unresectable carcinoid tumors. Methods: Patients on a stable dose of octreotide were randomly assigned to therapy with BVZ or PEGI for 18 weeks. After 18 weeks, the patients receive both drugs. Functional CT was used to monitor changes in blood flow (BF), blood volume (BV), and permeability surface (PS). PFS durations, calculated by Kaplan Meier method, were compared by log rank test. Results: Planned accrual of 44 patients is complete. 41 (20 BVZ, 21 PEGI) have completed at least 9 weeks of therapy. 35 (18 BVZ, 17 PEGI) patients have completed 18 weeks of octreotide plus BVZ or PEGI. We have previously reported decreased in tumor perfusion within 48 hours of treatment with BVZ by functional CT (ASCO 2004 abstr # 3013). We now also reported sustained decrease in tumor perfusion at week 18 (21 days after the previous dose of bevacizumab). By RECIST criteria, 3 PR (3 BVZ, 0 PEGI), 31 SD (16 BVZ, 15 PEGI), 6 PD (1 BVZ, 5 PEGI) have been observed. An additional patient achieved PR on BVZ + PEGI following PD on PEGI alone. Twenty-two patients remain on study. PFS duration was superior in the BVZ arm (P=.01). PFS rates after 18 weeks of monotherapy were 95% in BVZ versus 67% in PEGI arm. During the 18 weeks of monotherapy, ≥ 50% reduction in 5HIAA was observed in 21% on BVZ and 43% on PEGI. Overall, 46% achieved ≥ 50% reduction in 5HIAA. Conclusions: BVZ therapy is associated with suppression of tumor blood flow and prolongation of PFS duration in carcinoid tumors. Addition of PEGI may help to control hormonal output in patients refractory to octreotide. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech