PMID- 25466509 OWN - NLM STAT- MEDLINE DCOM- 20150417 LR - 20181202 IS - 1879-0852 (Electronic) IS - 0959-8049 (Linking) VI - 51 IP - 1 DP - 2015 Jan TI - Time course of safety and efficacy of aflibercept in combination with FOLFIRI in patients with metastatic colorectal cancer who progressed on previous oxaliplatin-based therapy. PG - 18-26 LID - S0959-8049(14)01055-7 [pii] LID - 10.1016/j.ejca.2014.10.019 [doi] AB - BACKGROUND: Patients with metastatic colorectal cancer (mCRC) previously-treated with oxaliplatin benefit significantly from the addition of aflibercept to FOLFIRI in relation to overall survival, progression-free survival and response rate. PATIENTS AND METHODS: The results for efficacy and safety over the time course of the VEGF Trap (aflibercept) with irinotecan in colorectal cancer after failure of oxaliplatin regimen trial were analysed based on data from 1226 patients randomised to receive FOLFIRI plus either aflibercept (n=612) or placebo (n=614). Hazard ratios (HR) by 6-month time period were estimated using a piecewise Cox proportional hazard model. Severity of adverse events (AEs) was graded using National Cancer Institute Common Terminology Criteria, version 3.0. RESULTS: The estimated probabilities of survival were 38.5% versus 30.9% at 18 months, 28.0% versus 18.7% at 24 months and 22.3% versus 12.0% at 30 months, for the aflibercept- and placebo-treated arms, respectively. The proportional improvement in the HR over time was consistent with the survival probability results; survival at 24 months was improved by 50% and almost doubled at 30 months. The majority of worst-grade AEs occurred within the first four cycles of treatment and in a small percent of treatment cycles and were mostly reversible. Common chemotherapy- and anti-vascular epithelial growth factor (VEGF)-associated AEs occurred rarely and in a small proportion of cycles with the majority being of single occurrence. CONCLUSIONS: The addition of aflibercept to FOLFIRI showed a continued and persistent improvement in overall survival over time in patients with mCRC. Although grade 3-4 AEs were more frequent in the aflibercept arm, they occurred in early treatment cycles and decreased sharply following initial presentation. CI - Copyright (c) 2014 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Ruff, Paul AU - Ruff P AD - University of Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa. Electronic address: pruff@iafrica.com. FAU - Ferry, David R AU - Ferry DR AD - Russells Hall Hospital, Dudley, UK. FAU - Lakomy, Radek AU - Lakomy R AD - Masaryk Memorial Cancer Institute, Brno, Czech Republic. FAU - Prausova, Jana AU - Prausova J AD - Fakultni nemocnice v Motole, Praha, Czech Republic. FAU - Van Hazel, Guy A AU - Van Hazel GA AD - University of Western Australia, Western Australia, Australia. FAU - Hoff, Paulo M AU - Hoff PM AD - Centro De Oncologia/Hospital Sirio Libanes, Sao Paulo, Brazil. FAU - Cunningham, David AU - Cunningham D AD - The Royal Marsden Hospital, Sutton, UK. FAU - Arnold, Dirk AU - Arnold D AD - Department of Medical Oncology, Tumor Biology Center, Freiburg, Germany. FAU - Schmoll, Hans J AU - Schmoll HJ AD - Martin Luther University Halle-Wittenberg, Germany. FAU - Moiseyenko, Vladimir M AU - Moiseyenko VM AD - Oncology Research Institute Na. NN. Petrov, St-Petersburg, Russian Federation. FAU - McKendrick, Joseph J AU - McKendrick JJ AD - Monash University, Victoria, Australia. FAU - Ten Tije, Albert J AU - Ten Tije AJ AD - Amphia Hospital, Breda, The Netherlands. FAU - Vishwanath, Raghu L AU - Vishwanath RL AD - Sanofi Global Oncology Medical Affairs, Cambridge, MA, United States. FAU - Bhargava, Pankaj AU - Bhargava P AD - Sanofi Global Oncology Research and Development, Cambridge, MA, United States. FAU - Chevalier, Soazig AU - Chevalier S AD - Sanofi, Vitry-sur-Seine, France. FAU - Macarulla, Teresa AU - Macarulla T AD - Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autonoma de Barcelona, Barcelona, Spain. FAU - Van Cutsem, Eric AU - Van Cutsem E AD - University Hospitals Leuven and KU Leuven, Belgium. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20141114 PL - England TA - Eur J Cancer JT - European journal of cancer (Oxford, England : 1990) JID - 9005373 RN - 0 (Biomarkers, Pharmacological) RN - 0 (Organoplatinum Compounds) RN - 0 (Recombinant Fusion Proteins) RN - 04ZR38536J (Oxaliplatin) RN - 15C2VL427D (aflibercept) RN - 7673326042 (Irinotecan) RN - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor) RN - Q573I9DVLP (Leucovorin) RN - U3P01618RT (Fluorouracil) RN - XT3Z54Z28A (Camptothecin) SB - IM MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/pharmacology/*therapeutic use MH - Biomarkers, Pharmacological MH - Camptothecin/adverse effects/*analogs & derivatives/pharmacology/therapeutic use MH - Colorectal Neoplasms/pathology MH - Disease Progression MH - Disease-Free Survival MH - Female MH - Fluorouracil/adverse effects/pharmacology/*therapeutic use MH - Humans MH - Irinotecan MH - Leucovorin/adverse effects/pharmacology/*therapeutic use MH - Male MH - Neoplasm Metastasis MH - Organoplatinum Compounds/*therapeutic use MH - Oxaliplatin MH - Proportional Hazards Models MH - Receptors, Vascular Endothelial Growth Factor/adverse effects/pharmacology/*therapeutic use MH - Recombinant Fusion Proteins/adverse effects/*therapeutic use OTO - NOTNLM OT - Aflibercept OT - Colorectal cancer OT - Efficacy OT - PlGF OT - Safety OT - VEGF-A OT - VEGF-B EDAT- 2014/12/04 06:00 MHDA- 2015/04/18 06:00 CRDT- 2014/12/04 06:00 PHST- 2014/03/17 00:00 [received] PHST- 2014/08/12 00:00 [revised] PHST- 2014/10/23 00:00 [accepted] PHST- 2014/12/04 06:00 [entrez] PHST- 2014/12/04 06:00 [pubmed] PHST- 2015/04/18 06:00 [medline] AID - S0959-8049(14)01055-7 [pii] AID - 10.1016/j.ejca.2014.10.019 [doi] PST - ppublish SO - Eur J Cancer. 2015 Jan;51(1):18-26. doi: 10.1016/j.ejca.2014.10.019. Epub 2014 Nov 14.