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, 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

Abstract

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.

Keywords: Aflibercept; Chemotherapy; Colorectal cancer; Irinotecan; Second-line.

Conflict of interest statement

Conflict-of-interest statement: Dr. Chibaudel has nothing to disclose.

Figures

Figure 1
Figure 1
Comparison of the FOLFIRI-1and FOLFIRI-3 schedules.
Figure 2
Figure 2
Flow diagram.
Figure 3
Figure 3
Progression-free survival and overall survival according to prior exposure to irinotecan (n = 65). A: Progression-free survival; B: Overall survival.

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