Phase II trial of FOLFOX plus bevacizumab in advanced, progressive neuroendocrine tumors

Abstract

15545 Background: Inhibitors of the VEGF pathway have been shown to have activity in neuroendocrine tumors (NET). Oxaliplatin- based chemotherapy also shows limited activity in this disease. We performed a prospective, phase II study to assess the safety and efficacy of mFOLFOX-6 plus bevacizumab (BV) in patients (pts) with advanced, progressive NET. Methods: Pts with carcinoid tumors (CARC), pancreatic NET (PNET), or platinum-refractory poorly differentiated (anaplastic, small- or large-cell) NET (PDNET) were enrolled using a Simon 2- stage design (3 groups). Eligibility criteria included clinical or radiologic evidence of progression, no prior anti-VEGF therapy, and no varices secondary to splenic vein thrombosis. Treatment consisted of mFOLFOX-6 plus BV (5 mg/kg IV) every 14 days (1 cycle = 2 weeks). Pts were followed for toxicity and response. Results: 13 pts with progressive NET have been enrolled: M/F=9/4; median age=60 (range 43–73); ECOG PS 0/1= 7/6; CARC/PNET/PDNET= 6/6/1. Pts on octreotide remained on the drug. Pts have received treatment for a median of 11 cycles (range 3–26). Grade 3–4 toxicities included: abdominal pain (15.4%), anemia (15.3%), neutropenia (30.8%), febrile neutropenia (7.6%), fatigue (38.4%), ascites (7.6%), gastrointestinal hemorrhage (7.6%), hypertension (23%), thrombocytopenia (7.6%), diarrhea (7.6%) and peripheral sensory neuropathy (15.3%). There was 1 arterial thromboembolic event (penetrating ulcer-thoracic aorta) and 1 treatment- related death from sepsis (in setting of neutropenia, diarrhea, and probable GI perforation). Of 9 pts with an elevated chromogranin at baseline; 4 pts demonstrated >50% decline (1 CARC, 3 PNET). One pt with metastatic insulinoma requiring home dextrose infusions experienced a >50% reduction in insulin levels and marked clinical improvement. 12 pts are evaluable for best radiologic response (by RECIST, confirmed): CARC 1/5 PR (20%), 4/5 SD (80%); PNET 2/6 PR (33%), 4/6 SD (67%); PDNET 1/1 SD. Conclusions: The combination of FOLFOX plus BV shows promising activity in pts with advanced, progressive NET. However, the toxicity profile suggests that careful pt selection may be important. Enrollment to this study continues. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology, sanofi-aventis Genentech™ BioOncology, sanofi-aventis