O-0010 - AXE BEAM: neo-adjuvant triplet versus doublet therapy with radiation and total mesorectal excision for locally advanced rectal cancer – a randomiz...

Date 27 June 2014
Event World GI 2014
Session Presentation of selected abstracts
Topics Anti-Cancer Agents & Biologic Therapy
Rectal Cancer
Surgery and/or Radiotherapy of Cancer
Presenter Gabriela Chiritescu
Citation Annals of Oncology (2014) 25 (suppl_2): ii105-ii117. 10.1093/annonc/mdu193
Authors G. Chiritescu1, L. Verbeke2, M. Polus3, J.F. Daisne4, J. Decaestecker5, A. D'Hoore1, F. Mardjuadi6, A. Debucquoy1, M. Verstraete1, X. Sagaert1, K. Haustermans1, K. Dumon1, P. Vergauwe7, J. Arts8
  • 1University Hospitals Leuven, Leuven/BE
  • 2Onze Lieve Vrouw Ziekenhuis Aalst, Aalst/BE
  • 3C.H.U. Sart-Tilman Liege, Liege/BE
  • 4Clinique Sainte Elisabeth Namur, Namur/BE
  • 5Heilig Hart Ziekenhuis Roeselare, Roeselare/BE
  • 6St-Luc University Hospital, Av, Brussels/BE
  • 7A.Z. Groeninge Kortrijk, Kortrijk/BE
  • 8A.Z. Sint Lucas Brugge, Brugge/BE

Abstract

Introduction

In an academic multicentric phase II study, patients (pts) with locally advanced rectal cancer were randomized to receive radiotherapy (1.8Gy/day) with the triplet bevacizumab (A 5mg/kg), capecitabine (X 1650 mg/m2/day) and oxaliplatin (E 50mg/m2) in Arm A or the doublet A + X without E in Arm B.

Methods

Chemoradiotherapy (CRT) started at 2 weeks after 1st infusion of A and continued for 5 weeks. Total mesorectal excision was planned at 6-8 weeks post CRT. Pathological complete response (pCR) rate in Arm A was the primary endpoint. Safety profile and identification of biomarkers for early response prediction were the secondary endpoints. Immunohistochemical staining for the functionality of blood vessels, proliferation and hypoxia, as well as Luminex analyses to assess the changes in circulating VEGF ligands are being performed on tissues and blood samples from consenting pts.

Results

Target recruitment was reached in September 2013. Eighty-four pts with median age 61 completed treatment, 82 including surgery, with a relative dose intensity of 98% for A and X and 93% for E. The CRT regimen was generally well tolerated. During CRT, serious adverse events (SAEs) were more frequent in Arm A vs. Arm B: fever (3 vs. 1), diarrhea (3 vs. 0), infection (5 vs. 1). Post-operative SAEs (wound infections, leaks) occurred in 17 pts, 10 in Arm A and 7 in Arm B. Five pts deceased post-study, 3 due to distant disease progression and 2 to post-operative complications. At the time of submission, post-surgery data were available for 76 pts. pCR was seen in 16 pts, 28% (12/43) in Arm A and 10% (4/41) in Arm B in an intent-to-treat analysis (ITT). The rate of good responders (Dworak TRG 3,4) was higher in Arm A (27/43) vs. Arm B (16/41) in ITT. Changes of the pericyte coverage of the blood vessels were observed and are being assessed. The decrease of plasma concentration of PDGF-AA and PDGF-BB seemed associated with a complete pathological response (p = 0.04 and p = 0.03 respectively).

Conclusion

Chemoradiotherapy in combination with bevacizumab showed and acceptable safety profile. The addition of oxaliplatin to capecitabine with bevacizumab and radiotherapy seems beneficial in terms of pathological complete response rates in our patient population, with a slight increase in toxicity. The main endpoint has been reached with 12/43 pCRs in Arm A. PDGF may be a predictor of response in this setting. Further analyses are ongoing and final data will be presented at the conference. Conducted with support from Roche and Sanofi Aventis.