FOLFIRI (5FU/leucovorin/irinotecan) + aflibercept significantly improves median overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) in patients (pts) with previously treated metastatic colorectal cancer (mCRC). The aim of this study was to investigate efficacy and tolerability of adding aflibercept to FOLFIRI in the first line setting.
Pts with untreated documented mCRC received aflibercept plus FOLFIRI every 14 days until progression or unacceptable toxicity in an open, phase II single arm, multicenter trial. The primary endpoint was the 6-months PFS rate. Secondary endpoints were overall PFS, OS and tolerability. A two- steps Simon design was used with H0: 55% and H1= 75%, respectively (one-sided α = 5%, 1-β=90%). Data were analyzed in intention to treat population. The study was stopped at the first stage.
41 patients were included and 40 analyzed (1 consent withdrawal) in 9 French centers between 10/2014 and 02/2017. Median age was 65 y (46-81), 42% were men, 53% had two or more metastatic sites. Eighteen patients (54.5%, IC [38.940; 69.509]) were alive and non-progressive at 6 months. Treatment with FOLFIRI plus aflibercept was therefore considered ineffective, inclusions were stopped. Median follow-up was 20.5 months (95% CI (15,11 ; 27,86)). ORR was 54% and disease control rate was 80%. Median duration of treatment was 5.2 months, median PFS and OS were 8,3 and 21.9 months respectively. Grade 3-4 adverse events were mainly gastrointestinal (18 pts, 45% : mucositis (15%), diarrhea (12,5%), abdominal pain (10%)) and vascular (13 pts, 32,5% : hypertension (17,5%) and venous thromboembolism (15%)). Severe hematological toxicities occurred in 7,5% of pts. 87.5% of patients had at least one dose modification during treatment. 37 pts received a second line therapy.
First line FOLFIRI+ aflibercept for mCRC pts is feasible but with significant toxicities leading to dose reduction in the majority of patients. Median PFS and OS were close to those reported with classical doublet and targeted agents in this setting.
Clinical trial identification
Legal entity responsible for the study
Fédération Francophone de Cancérologie Digestive.
S. Pernot: Honoraria: Amgen, Sanofi; Travel, accomodations, expenses: Amgen, Merck, Servier, Bayer T. Aparicio: Conference: Pfizer, Roche, Sanofi, Léo Pharma, Amgen, BMS, Servier, Shire, Ipsen; Board: Pierre Fabre Ipsen, HalioDX, BMS; Travels: Ipsen, Novartis, Roche, Hospira; Research: Novartis. L. Dahan: Honoraria: Sanofi, Amgen. T. Lecomte: Consultant, expert: Sanofi; Courses, trainings: Lilly, Merck, Amgen; Invitations to national or international congresses: Amgen C. Lepage: Clinical research: Ipsen, Novartis Oncology; Courses: Advanced Accelerator Applications; Invitations to national or international congresses: Amgen, Ipsen, Novartis Oncology, Bayer. J. Taieb: Consultancy: Roche, Merck KGaA, Amgen, Celgene, Lilly, Baxalta, Servier, Sirtex Medical; Speaker's bureau: Servier, Amgen, Baxalta, Roche/Genentech, Sanofi, Merck, Lilly. All other authors have declared no conflicts of interest.