567P - Neoadjuvant Multidisciplinary Phase II Study (BRANCH) of an Early Bevacizumab Schedule Plus Chemo-Radiation Therapy in Rectal Cancer: Efficacy, Safety, and Biomarkers

Abstract

ABSTRACT Background In BRANCH study we assess the safety and efficacy of an experimental schedule of early (4 days before) bevacizumab (BEV) added to neoadjuvant chemotherapy (CT) and radiotherapy (RT) in poor-risk locally advanced rectal cancer (pLARC) patients (pts) and explore the potential of circulating endothelial cells (CECs) and tumor lesion glycolysis (TLG) as surrogate markers of pathological response(PR). Patients and methods 46 pts (cT4, cN + , cT3≤ 5 cm from the anal verge and/or positive circumferential margin, M1 resectable) received 3 biweekly courses of oxaliplatin (100 mg/m2)/raltitrexed (2.5 mg/m2) on day 1, and 5-FU (800 mg/m2)/folinic acid (250 mg/m2) on day 2 during pelvic RT (45 Gy). BEV (5 mg/kg) was given biweekly 4 days before beginning of CT/RT for 2 courses. Toxicity was graded with NCI-CTC v.3. PR was defined using Mandard tumor regression grade (TRG). According to the Simon's two-stage design, assuming an hypothesis of a 50% TRG1 (complete tumor regression) (α error = 0.05, β error = 0.20), at least 6/16 TRG1 should be obtained to continue accrual to 46 pts. CECs and TLG were evaluated at baseline (BL) on day 10 and before surgery, by flow cytometry and FDG-PET, respectively. Statistical analysis was by Mann-Whitney test. Results We obtained 23 TRG1 (50%), 14 TRG2 (30%) and 8 TRG3-4 (17%). Grade ¾ neutropenia was the most common adverse event (13/46 pts, 28%). TLG reduction on day 10 vs BL was significantly higher in responders TRG1-2 compared to non-responders TRG3-4 pts (median -72%, range -90% + 31% vs -38%, range -45% + 25%; p Conclusions Current scheme of BEV plus CT and RT appears safe and active, yielding high rate of TRG1 and TRG2 responses in pLARC. Early FDG-PET and CECs evaluation emerged as potential biomarkers for treatment selection to be incorporated in design of future studies with this regimen. CEP and citochine data will be provided at the meeting. Disclosure All authors have declared no conflicts of interest.