Copyright
©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
FOLFIRI3-aflibercept in previously treated patients with metastatic colorectal cancer
Candice Carola, François Ghiringhelli, Stefano Kim, Thierry André, Juliette Barlet, Leïla Bengrine-Lefevre, Hélène Marijon, Marie-Line Garcia-Larnicol, Christophe Borg, Linda Dainese, Nils Steuer, Hubert Richa, Magdalena Benetkiewicz, Annette K Larsen, Aimery de Gramont, Benoist Chibaudel
Candice Carola, Juliette Barlet, Hélène Marijon, Aimery de Gramont, Benoist Chibaudel, Department of Medical Oncology, Franco-British Institute, Levallois-Perret 92300, France
François Ghiringhelli, Leïla Bengrine-Lefevre, Department of Medical Oncology, Centre George François Leclerc, Dijon 21000, France
Stefano Kim, Christophe Borg, Department of Medical Oncology, CHU Besançon, Besançon 25030, France
Thierry André, Marie-Line Garcia-Larnicol, Nils Steuer, Department of Medical Oncology, Saint-Antoine Hospital, and Sorbonne Universités, UMPC, Paris 75012, France
Linda Dainese, Department of Anatomy-Pathology, Paris Pathology Institute, Malakoff 92240, France
Hubert Richa, Department of Gastrointestinal Surgery, Franco-British Institute, Levallois-Perret 92300, France
Magdalena Benetkiewicz, Fondation ARCAD, Levallois-Perret 92300, France
Annette K Larsen, Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, INSERM U938, Faculté de Médecine Sorbonne Université, Paris 75012, France
Author contributions: Carola C, Barlet J and Chibaudel B completed the data collection and prepared the manuscript; Carola C, de Gramont A and Chibaudel B analyzed the data; all authors had read and approved manuscript.
Institutional review board statement: This study was reviewed and approved by the Institutional Review Committee in Cancer Research (IRCCR) of Franco-British Hospital (FBI). Personal and filiation data including identity of every patient was protected with an added code in the Excel table. This is a retrospective case series that did not have any activity or contact with the patients.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment.
Conflict-of-interest statement: Dr. Chibaudel has nothing to disclose.
STROBE statement: The authors have read the STROBE Statement and the manuscript was prepared and revised according to the STROBE Statement.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Benoist Chibaudel, MD, Department of Medical Oncology, Franco-British Institute, 4 rue Kléber, Levallois-Perret 92300, France.
benoist.chibaudel@ihfb.org
Telephone: +33-14-7591923
Received: March 30, 2018
Peer-review started: March 30, 2018
First decision: May 2, 2018
Revised: June 11, 2018
Accepted: June 28, 2018
Article in press: June 28, 2018
Published online: September 14, 2018
Processing time: 168 Days and 2.8 Hours
ARTICLE HIGHLIGHTS
Research background
FOLFIRI3 is the second-line regimen of choice in patients with previously treated mCRC in some centers. Adding bevacizumab to FOLFIRI3 has shown promising efficacy results in two prior retrospective trials. The addition of aflibercept to FOLFIRI in patients with pretreated mCRC increased response rate from 11% to 20% and improved median PFS from 4.7 to 6.9 mo.
Research motivation
The phase III VELOUR and non-randomized FOLFIRI3 studies results provide a backbone for our study.
Research objectives
The main objective of the study is to evaluate the safety and efficacy of the FOLFIRI3-aflibercept combination as second or later-line therapy in patients with mCRC.
Research methods
Patients with previously treated mCRC were given the aflibercept-FOLFIRI3 combination and were divided into “irinotecan-naive” population including patients with no more than one prior line of treatment for metastatic disease, and the “irinotecan pre-exposed” population including patients for whom the number of prior treatment lines for metastatic disease was not restricted. The primary endpoint was overall response rate (ORR). Secondary endpoints were disease control rate, progression-free survival (PFS), overall survival (OS), and safety. Toxicity was evaluated according to the United States National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03.
Research results
Minimally modified FOLFIRI has improvement dramatically the efficacy of the FOLFIRI3-aflibercept combination with high response rates (43% in irinotecan-naïve patients and 34% in irinotecan pre-exposed patients) and survivals (median PFS: 11.3 mo, OS: 17.0 mo and PFS: 5.7 mo and OS: 14.3 mo, respectively) in patients with previously treated mCRC, whatever prior use of irinotecan.
Research conclusions
The combination of aflibercept and FOLFIRI3 shows encouraging efficacy results in patients with previously treated mCRC.
Research perspectives
A prospective randomized trial is planned to compare FOLFIRI-aflibercept to FOLFIRI3-aflibercept.
