Randomized Phase 2 Study Comparing Pathological Responses of Resected Colorectal Cancer Metastases after Bevacizumab with mFOLFOX6 or FOLFIRI (BEV-ONCO Trial).
bevacizumab; chemotherapy; colorectal liver metastases; histological growth pattern; pathological response; tumoral homogeneity; Oncology; Cancer Research
Abstract :
[en] Retrospective studies reported that preoperative oxaliplatin-based chemotherapy increased pathological response (PR) in patients resected for colorectal liver metastases (CRLM). This multicenter prospective randomized (1/1) phase II trial evaluated PR on resected CRLM after preoperative mFOLFOX6 (arm A) or FOLFIRI (arm B) + bevacizumab. The primary endpoint was the major pathological response rate (MPRR), defined as the percentage of patients presenting CRLMs with mean tumor regression grade (TRG) < 3. Secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). Out of 65 patients, 57 patients (28 and 29 in arm A/B) were resected for CRLM (one patient with lung metastases). Clinical and treatment characteristics were similar in both arms. One-month postoperative complications were 39.3%/31.0% in arm A/B (p = 0.585). MPRR and complete PR were 32.1%/20.7% (p = 0.379) and 14.3%/0.0% (p = 0.052) in arm A/B, respectively. PFS and OS were not different. Patients with PR among all CRLMs (max TRG ≤ 3; 43.8% of patients) had a lower risk of relapse (PFS: HR = 0.41, 95%CI = 0.204−0.840, p = 0.015) and a tendency towards better survival (OS: HR = 0.34, 95%CI = 0.104−1.114, p = 0.075). The homogeneity of PR was associated with improved PFS/OS. This trial fails to demonstrate a significant increase in MPRR in patients treated with mFOLFOX6-bevacizumab but confirms PR as an important prognostic factor.
Disciplines :
Oncology
Author, co-author :
Baldin, Pamela; Pathology Department, Cliniques Universitaires Saint Luc (UCL)-Université Catholique de Louvain, 1200 Bruxelles, Belgium
Carrasco, Javier; Department of Medical Oncology, GHdC-Grad Hopital de Charleroi-Site Notre Dame, 6000 Charleroi, Belgium
Beniuga, Gabriela; Pathology Department, Institut de Pathologie et Génétique, 6041 Gosselies, Belgium
Jouret-Mourin, Anne; Pathology Department, Cliniques Universitaires Saint Luc (UCL)-Université Catholique de Louvain, 1200 Bruxelles, Belgium ; Pathology Department, Institut de Pathologie et Génétique, 6041 Gosselies, Belgium
Demolin, Gauthier ; Université de Liège - ULiège > Département des sciences cliniques
Delos, Monique; Pathology Department, CHU-UCL-Namur, Site Godinne, 5530 Yvoir, Belgium
Castella, Marie-Laure; Colorectal Clinical Research Unit, Institut Roi Albert II, Cliniques Universitaires Saint Luc (UCL)-Université Catholique de Louvain, 1200 Bruxelles, Belgium
van Maanen, Aline ; Support Statistique, Institut Roi Albert II, Cliniques Universitaires Saint Luc (UCL)-Université Catholique de Louvain, 1200 Bruxelles, Belgium
Van den Eynde, Marc ; Department of Medical Oncology and Gastroenterology, Cliniques Universitaires Saint Luc (UCL)-Université Catholique de Louvain, 1200 Bruxelles, Belgium
Randomized Phase 2 Study Comparing Pathological Responses of Resected Colorectal Cancer Metastases after Bevacizumab with mFOLFOX6 or FOLFIRI (BEV-ONCO Trial).
Funding: We received a restricted research grant from ROCHE (NV Roche SA, Rue Dantestraat 75, 1070 Brussels Belgium) to conduct this study (funding number Ro 4876646, ML28669, BEV-ONCO2012). The funder had no role in the study design; in the collection, analysis or interpretation of data; in the writing of the manuscript and the decision to submit this article for publication.
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