A Phase II Trial of Bevacizumab Combined with Chemotherapy in Patients with Metastatic Well-Differentiated Duodeno-Pancreatic Endocrine Tumors (Better Study)

ABSTRACT Background We assessed bevacizumab (Bv), a monoclonal antibody targeting VEGF, in combination with chemotherapy in duodeno-pancreatic NET, in a multicenter, open-label, non-randomized, two-group phase II trial. Demographics and primary endpoint (PFS) will be presented at ASCO 2012 (abstract # 4036). Here we emphasize on response centralized review, PP analysis and safety data. Methods Patients (pts) with progressive, metastatic, well-differentiated duodeno-pancreatic NET (WHO 2000), ECOG PS ≤2 and Ki 67 index  Results In the ITT population (n = 34), 22 (64.7%) pts were men, median age 55.3 years (37.0-77.6), ECOG-PS was 0/1 in 33 pts (97.1%). Ki-67 proliferative index was between 3 - 15% in 75.0% of pts. After a maximum of 24 months of follow-up per patient, median PFS assessed by investigators was 23.7 months [95%CI: 13.1; not reached] based on 18 events. Centralized review of tumor control rate was 100% (n= 33; 1 missing) including partial response in 17 (51.5%) pts and stable disease in 16 (48.5%) pts; similarly to investigators assessments. Survival rate at 24 months was 88%. Median OS was not reached. All efficacy results were comparable in the ITT and PP populations. All patients experienced at least one adverse event (AE). CTC grade 3/4 AEs occurred in 23 (67.6%) of pts, mainly digestive 5 (14.7%) pts (abdominal pain, 4 pts). G3/4 AEs of special interest to BV were hypertension in 7 (20.6%) pts and thromboembolism in 3 (8.8%), all venous. No grade 3/4 proteinuria was observed. Five patients died (4 of disease progression and 1 of thromboembolic event). Conclusions Efficacy results of Bv and 5-FU/stz, a novel approach in duodeno-pancreatic NET, are encouraging. The toxicity profile of the combination of Bv with streptozocin is acceptable and did not induce any unexpected events. These results warrant to be confirmed in a phase III study. Disclosure M.P. Ducreux: Consultant: Roche, Merck Serono Honoraries: Roche, Merck Serono, Amgen, Bayer, Fresenus, Pfizer, Sanofi Clinical research project: Pfizer, Chugai, Merck Serono. J. Seitz: Consultant: Keocyt Honoraries: Roche, Pfizer. C. Dromain: Consultant: Roche Honoraries: Roche. A. Gorana: Employment: Roche. E. Mitry: Honoraries: Roche. All other authors have declared no conflicts of interest.