AXE BEAM: ENCOURAGING EARLY RESULTS OF A NEO-ADJUVANT BEVACIZUMAB, CAPECITABINE +/- OXALIPLATIN AND RADIATION MULTIMODALITY REGIMEN FOR LOCALLY ADVANCED RECTAL CANCER

ABSTRACT In an academic multicentric phase II study, patients (pts) with locally advanced rectal cancer are randomized to receive bevacizumab (5mg/kg), capecitabine (1650mg/m2/day) and radiotherapy (1.8Gy/day) with (Arm A) or without (Arm B) oxaliplatin (50mg/m2). Chemoradiotherapy (CRT) starts at 2 weeks after 1st infusion of bevacizumab and continues for 5 weeks. Total mesorectal excision is planned at 6-8 weeks post CRT. Immunohistochemical staining to study the functionality of blood vessels and Luminex analyses to assess the changes in circulating VEGF ligands are performed on tissues and blood samples from consenting pts. Pathological complete response (pCR) rate, safety profile and identification of biomarkers for early response prediction are the main endpoints. Results Sixty five pts with median age 60 have been enrolled to date. Fifty seven pts completed the full protocol scheme, with a relative dose intensity of 97% for bevacizumab, 95% for capecitabine and 93% for oxaliplatin. Preliminary safety data from 60 evaluable pts show that the regimen is generally well tolerated. Most severe adverse events were post-operative (wound infections, leaks) in 9 pts, equally distributed between arms. During CRT, grade 3 toxicities were more frequent in Arm A: fatigue (1), diarrhea (2), infection (2), febrile neutropenia (1), sensory neuropathy (1). Two pts deceased due to disease progression and one due to lung embolism post-surgery. Fifty two pts are evaluable for response. pCR was seen in 11 pts, 30% (8/26) in Arm A and 12% (3/26) in Arm B (p = 0.08). The rate of good responders (Dworak TRG 3,4) was higher in Arm A 18/26 versus Arm B 10/26 (p = 0.05). Changes in the pericyt coverage of the blood vessels, proliferation of the tumour cells and plasma concentrations of PDGF-AA, PDGF-BB and VEGF were observed and will be further assessed. Conclusions Chemoradiotherapy in combination with bevacizumab showed an acceptable safety profile in this patient population. Adding oxaliplatin determined a slight increase of toxicity but might enhance the percentage of responders. PDGF may be a predictor of response in this setting. Further analyses are ongoing. Conducted with support from Roche and Sanofi Aventis. Disclosure K. Haustermans: The author has received research funding from Roche. E. Van Cutsem: The author has received research funding by Roche and Sanofi Aventis. All other authors have declared no conflicts of interest.