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
AIM
To evaluate the efficacy and safety of the modified FOLFIRI3-aflibercept as second-line therapy in patients with metastatic colorectal cancer.
METHODS
This is a retrospective multicenter cohort, evaluating the efficacy and safety of the association of aflibercept with FOLFIRI3 (day 1: aflibercept 4 mg/kg, folinic acid 400 mg/m2, irinotecan 90 mg/m2, 5-fluorouracil infusion 2400 mg/m2 per 46 h; day 3: irinotecan 90 mg/m2) in patients with previously treated metastatic colorectal cancer. The primary endpoint was overall response rate (ORR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.
RESULTS
Among 74 patients treated in four French centers, nine were excluded due to prior use of aflibercept (n = 3), more than one prior treatment line in irinotecan-naïve patients (n = 3), and inadequate liver function (n = 3). In the “irinotecan-naïve” patients (n = 30), ORR was 43.3% and DCR was 76.7%. Median PFS and OS were 11.3 mo (95%CI: 6.1-29.0) and 17.0 mo (95%CI: 13.0-17.3), respectively. The most common (> 5%) grade 3-4 adverse events were diarrhea (37.9%), neutropenia (14.3%), stomatitis and anemia (10.4%), and hypertension (6.7%). In the “pre-exposed irinotecan” patients (n = 35), 20 (57.1%) received ≥ 2 prior lines of treatment. ORR was 34.3% and DCR was 60.0%. Median PFS and OS were 5.7 mo (95%CI: 3.9-10.4) and 14.3 mo (95%CI: 12.8-19.5), respectively.
CONCLUSION
Minimally modified FOLFIRI has improvement dramatically the FOLFIRI3-aflibercept efficacy, whatever prior use of irinotecan. A prospective randomized trial is warranted to compare FOLFIRI-aflibercept to FOLFIRI3-aflibercept.
Core tip: Results obtained in this retrospective study show that minimally modified FOLFIRI has improvement dramatically the efficacy of the FOLFIRI3-aflibercept combination with high response rates and survivals in patients with previously treated metastatic colorectal cancer, whatever prior use of irinotecan. A prospective randomized trial is planned to compare FOLFIRI-aflibercept to FOLFIRI3-aflibercept.
