Randomized run-in study of bevacizumab (B) and everolimus (E) in low- to intermediate-grade neuroendocrine tumors (LGNETs) using perfusion CT as functional biomarker.

4002 Background: Studies have shown promising results for mTOR inhibitor, E, and VEGF inhibitor, B, in LGNETs. In our prior study, decrease in tumor blood flow (BF) following B was proportional to baseline BF suggesting B decreased BF by a fixed percentage. Methods: LGNET patients with lesion(s) ≥ 3 cm were randomized to therapy with B or E for one 21-day cycle. On cycle 2 day 1, the alternate agent was added (B+E). Functional CTs (fCTs) assessing tumor BF, blood volume (BV), mean transit time (MTT), and permeability surface (PS) were mandatory. Primary objectives were to determine the effects of B or E as well as B+E on BF. Response was evaluated by RECIST every 9 weeks. Results: 112 fCTs were performed among 39 eligible (treated) patients. 64 lesions among 36 patients were evaluated at 3 time points. B alone led to a 32% decrease in BF (p<0.01) and no significant change in MTT. E alone was associated with increase in MTT (13%; p=0.02) but not with decrease in BF. Addition of E to B led to a further decr...